/****************************************************************************
 * Copyright (C) 2009-2015 EPAM Systems
 * 
 * This file is part of Indigo toolkit.
 * 
 * This file may be distributed and/or modified under the terms of the
 * GNU General Public License version 3 as published by the Free Software
 * Foundation and appearing in the file LICENSE.GPL included in the
 * packaging of this file.
 * 
 * This file is provided AS IS with NO WARRANTY OF ANY KIND, INCLUDING THE
 * WARRANTY OF DESIGN, MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE.
 ***************************************************************************/

#include "molecule/molecule_ionize.h"
#include "molecule/base_molecule.h"
#include "molecule/elements.h"
#include "molecule/molecule.h"
#include "molecule/smiles_loader.h"
#include "molecule/molfile_loader.h"
#include "molecule/molfile_saver.h"
#include "base_cpp/scanner.h"
#include "molecule/query_molecule.h"
#include "molecule/molecule_substructure_matcher.h"
#include "base_cpp/output.h"
#include "molecule/sdf_loader.h"
#include "base_cpp/queue.h"
#include "molecule/molecule_automorphism_search.h"

using namespace indigo;

MoleculePkaModel MoleculePkaModel::_model;

IMPL_ERROR(MoleculePkaModel, "Molecule Pka Model");

MoleculePkaModel::MoleculePkaModel ()
{
//   _loadSimplePkaModel();
//   _loadAdvancedPkaModel();
}

void MoleculePkaModel::estimate_pKa (Molecule &mol, const IonizeOptions &options, Array<int> &acid_sites,
                      Array<int> &basic_sites, Array<float> &acid_pkas, Array<float> &basic_pkas)
{
   if (options.model == IonizeOptions::PKA_MODEL_SIMPLE)
   {
      if (!_model.simple_model_ready)
         _loadSimplePkaModel();  
      _estimate_pKa_Simple(mol, options, acid_sites, basic_sites, acid_pkas, basic_pkas);
   }
   else if (options.model == IonizeOptions::PKA_MODEL_ADVANCED)
   {
      if (!_model.advanced_model_ready)
         _loadAdvancedPkaModel();  
      _estimate_pKa_Advanced(mol, options, acid_sites, basic_sites, acid_pkas, basic_pkas);
   }
   else
      throw Error("Unsupported pKa model: %d", options.model);
}

int MoleculePkaModel::buildPkaModel (int max_level, float threshold, const char * filename)
{
//   QS_DEF(Array<int>, order);
//   QS_DEF(Molecule, can_mol);
   QS_DEF(Array<char>, fp);
   RedBlackStringObjMap<Array <float> > acid_pkas;
   RedBlackStringObjMap<Array <float> > basic_pkas;
   RedBlackStringObjMap<Array <int> > acid_pka_cids;
   RedBlackStringObjMap<Array <int> > basic_pka_cids;
   AromaticityOptions opts;

   const char * a_pka_sites_id = "ACID PKA SITES";
   const char * a_pka_values_id = "ACID PKA VALUES";
   const char * b_pka_sites_id = "BASIC PKA SITES";
   const char * b_pka_values_id = "BASIC PKA VALUES";
   const char * compound_cid = "PUBCHEM_COMPOUND_CID";

   Molecule mol;
   int level = 0;

   _model.adv_a_pkas.clear();
   _model.adv_b_pkas.clear();

   for (;;)
   {
      FileScanner scanner(filename);
      SdfLoader loader(scanner);

      int a_count = 0;
      int b_count = 0;
      acid_pkas.clear();
      basic_pkas.clear();
      acid_pka_cids.clear();
      basic_pka_cids.clear();

      int mol_count = 0;
      while (!loader.isEOF())
      {
         mol_count++;
         loader.readNext();
         BufferScanner scanner(loader.data);
         MolfileLoader mol_loader(scanner);
         mol_loader.stereochemistry_options.ignore_errors = true;
         mol_loader.loadMolecule(mol);

         int cid = 0;
         if (loader.properties.contains(compound_cid))
         {
            BufferScanner scan_cid(loader.properties.at(compound_cid));
            cid = scan_cid.readInt();
         }


//         mol.aromatize(opts);
//         _checkCanonicalOrder(mol, can_mol, order);
         _removeExtraHydrogens(mol);

         if (loader.properties.contains(a_pka_sites_id))
         {
            const char *aids = loader.properties.at(a_pka_sites_id);
            const char *apkas = loader.properties.at(a_pka_values_id);

            BufferScanner scan_aids(aids);
            Array<int> a_sites;
            while (!scan_aids.isEOF())
            {
              int idx = scan_aids.readInt1() - 1;
              a_sites.push(idx);
            }
            BufferScanner scan_apka(apkas);
            Array<float> a_pka;
            while (!scan_apka.isEOF())
            {
              float val = scan_apka.readFloat();
              a_pka.push(val);
            }

            if (a_sites.size() > 1)
            {
//               printf("Warning: multiple acid sites detected. Skip this compound (%d)\n", cid);
            }
            else
            {
               for (int i = 0; i < a_sites.size(); i++)
               {
                  fp.clear();
//                  int idx = order.find(a_sites[i]);
                  int idx = a_sites[i];
                  float val = a_pka[i];
      
                  getAtomLocalFingerprint (mol, idx, fp, level);
        
                  if (fp.size() == 0)
                     continue;
         
                  if (!acid_pkas.find(fp.ptr()))
                  {
                     acid_pkas.insert(fp.ptr());
                     acid_pka_cids.insert(fp.ptr());
                     a_count++;
                  }
                  acid_pkas.at(fp.ptr()).push(val);
                  acid_pka_cids.at(fp.ptr()).push(cid);
               }
            }
         }
   
         if (loader.properties.contains(b_pka_sites_id))
         {

            const char *bids = loader.properties.at(b_pka_sites_id);
            const char *bpkas = loader.properties.at(b_pka_values_id);
      
            BufferScanner scan_bids(bids);
            Array<int> b_sites;
            while (!scan_bids.isEOF())
            {
              int idx = scan_bids.readInt1() - 1;
              b_sites.push(idx);
            }
            BufferScanner scan_bpka(bpkas);
            Array<float> b_pka;
            while (!scan_bpka.isEOF())
            {
              float val = scan_bpka.readFloat();
              b_pka.push(val);
            }

            if (b_sites.size() > 1)
            {
//               printf("Warning: multiple protonation sites detected. Skip this compound (%d)\n", cid);
            }
            else
            {
               for (int i = 0; i < b_sites.size(); i++)
               {
                  fp.clear();
//                  int idx = order.find(b_sites[i]);
                  int idx = b_sites[i];
                  float val = b_pka[i];
      
                  getAtomLocalFingerprint (mol, idx, fp, level);
         
                  if (fp.size() == 0)
                     continue;
         
                  if (!basic_pkas.find(fp.ptr()))
                  {
                     basic_pkas.insert(fp.ptr());
                     basic_pka_cids.insert(fp.ptr());
                     b_count++;
                  }
                  basic_pkas.at(fp.ptr()).push(val);
                  basic_pka_cids.at(fp.ptr()).push(cid);
               }
            }
         }
      }

      bool model_ready = true;
      float max_deviation = 0.f;
   
      for (int i = 0; i < acid_pkas.size(); i++)
      {
         const char * fp = acid_pkas.key(i);
         Array<float> &pkas = acid_pkas.value(i);
         Array<int> &cids = acid_pka_cids.value(i);
         float pka_sum = 0.f;
         float pka_dev = 0.f;
         float pka_min = 100.f;
         float pka_max = -100.f;
         for (int k = 0; k < pkas.size(); k++)
         {
            float val = pkas.at(k);
            pka_sum = pka_sum + val;
            if (pka_min > val)
               pka_min = val;
            if (pka_max < val)
               pka_max = val;
         }

         if ((pka_max - pka_sum/pkas.size()) > (pka_sum/pkas.size() - pka_min))
            pka_dev = pka_max - pka_sum/pkas.size();
         else
            pka_dev = pka_sum/pkas.size() - pka_min;

         if (pka_dev > max_deviation)
            max_deviation = pka_dev;
           

         if (_model.adv_a_pkas.find(fp))
             _model.adv_a_pkas.remove(fp);
         _model.adv_a_pkas.insert(fp);
         _model.adv_a_pkas.at(fp).push(pka_sum /pkas.size());
         _model.adv_a_pkas.at(fp).push(pka_dev);

//         printf("      {PKA_ACID, \"%s\", %5.2f, %4.2f},\n", fp, pka_sum/pkas.size(), pka_dev);

/*
         for (int k = 0; k < cids.size(); k++)
         {
            printf("%d ", cids.at(k));
            printf("\n");
         }
*/ 
         if (pka_dev > threshold) 
            model_ready = false;
      }
      
      for (int i = 0; i < basic_pkas.size(); i++)
      {
         const char * fp = basic_pkas.key(i);
         Array<float> &pkas = basic_pkas.value(i);
         Array<int> &cids = basic_pka_cids.value(i);
         float pka_sum = 0.f;
         float pka_dev = 0.f;
         float pka_min = 100.f;
         float pka_max = -100.f;
         for (int k = 0; k < pkas.size(); k++)
         {
            float val = pkas.at(k);
            pka_sum = pka_sum + val;
            if (pka_min > val)
               pka_min = val;
            if (pka_max < val)
               pka_max = val;
         }

         if ((pka_max - pka_sum/pkas.size()) > (pka_sum/pkas.size() - pka_min))
            pka_dev = pka_max - pka_sum/pkas.size();
         else
            pka_dev = pka_sum/pkas.size() - pka_min;


         if (pka_dev > max_deviation)
            max_deviation = pka_dev;

         if (_model.adv_b_pkas.find(fp))
            _model.adv_b_pkas.remove(fp);
         _model.adv_b_pkas.insert(fp);
         _model.adv_b_pkas.at(fp).push(pka_sum / pkas.size());
         _model.adv_b_pkas.at(fp).push(pka_dev);
           
//         printf("      {PKA_BASIC, \"%s\", %5.2f, %4.2f},\n", fp, pka_sum/pkas.size(), pka_dev);

/*
         for (int k = 0; k < cids.size(); k++)
         {
            printf("%d ", cids.at(k));
            printf("\n");
         }
*/  
         if (pka_dev > threshold) 
            model_ready = false;
      }
/*   
      printf("Model level = %d, number of molecules in model file  = %d\n", level, mol_count);
      printf("                  number of unique acid fingeprints  = %d\n", a_count);
      printf("                  number of unique basic fingeprints = %d\n", b_count);
      printf("                  number of acid fingeprints included  = %d\n", _model.adv_a_pkas.size());
      printf("                  number of basic fingeprints included = %d\n", _model.adv_b_pkas.size());
      printf("                  maximum deviation for model          = %4.2f\n", max_deviation);
*/
      if (model_ready)
      {
         break;
      }
      else
      {
         if (level >= max_level)
         {
            level = -1;
            break;
         }
         else
         {
            level++;
            _model.max_deviations.push(max_deviation);
         }
      }
   }

   _model.level = level;
   _model.advanced_model_ready = true;

   return level;
}


void MoleculePkaModel::_loadSimplePkaModel()
{
   struct _PkaDef
   {
      const char *acid;
      float pka;
      const char *basic;
   };

   /*  Roger Sayle, Physiological ionization and pKa prediction,
   *   http://www.daylight.com/meetings/emug00/Sayle/pkapredict.html
   */
   static _PkaDef simple_pka_model[] = 
   {
      {"[F;!H0]", 3.18f, "[F-]"},
      {"[Cl;!H0]", -6.50f, "[Cl-]"},
      {"[Br;!H0]", -8.50f, "[Br-]"},
      {"[I;!H0]", -9.00f, "[I-]"},
      {"[c;!H0]", 43.00f, "[c-]"},
      {"[$([C]#N);!H0]", 9.30f, "[$([C-]#N)]"},
      {"[C;!H0]", 50.00f, "[C-]"},
      {"[nH;!H0]", 16.50f, "[n-]"},
      {"[$([N]=N=*);!H0]", -99.99f, "[$([N-]=N=*)]"},
      {"[$([N]C=O);!H0]", 22.00f, "[$([N-]C=O)]"},
      {"[$([N]S(=O)=O);!H0]", 10.10f, "[$([N-]S(=O)=O)]"},
      {"[N;!H0]", 32.50f, "[N-]"},
      {"[nH2+;!H0]", -3.80f, "[nH]"}, 
      {"[nH+;!H0]", 5.23f, "[n]"},
      {"[$([NH+]#*);!H0]", -12.00f, "[$([N]#*)]"},
      {"[$([NH+]=C(N)N);!H0]", 14.4f, "[$([N]=C(N)N)]"},
      {"[$([NH+]=C(N)a);!H0]", 11.6f, "[$([N]=C(N)a)]"},
      {"[$([NH+]=CN);!H0]", 12.4f, "[$([N]=CN)]"},
      {"[$([NH+]=*);!H0]", -99.99f, "[$([N]=*)]"},
      {"[$([NH+]a);!H0]", 4.69f, "[$([N]a)]"},
      {"[$([NH+]C=O);!H0]", 4.74f, "[$([N]C=O)]"},
      {"[$([NH+]C=N);!H0]", -99.99f, "[$([N]C=N)]"},
      {"[$([NH+]S(=O)=O);!H0]", -99.99f, "[$([N]S(=O)=O)]"},
      {"[NH+;!H0]", 10.5f, "[N]"},
      {"[NH2+;!H0]", 11.1f, "[$([N](C)C)]"},
      {"[NH3+;!H0]", 10.6f, "[NH2]"},
      {"[NH4+;!H0]", 9.25f, "[NH3]"},
      {"[OH2;!H0]", 15.70f, "[OH-]"},
      {"[$([O]c);!H0]", 10.00f, "[O-]a"},
      {"[$([O]C(=O)[O-]);!H0]", 10.33f, "[$([O-]C(=O)[O-])]"},
      {"[$([O]C(=O)a);!H0]", 4.20f, "[$([O-]C(=O)a)]"},
      {"[$([O]C=O);!H0]", 4.80f, "[$([O-]C=O)]"},
      {"[$([O]C);!H0]", 15.50f, "[$([O-]C)]"},
      {"[$([O]N(=O)=O);!H0]", -1.40f, "[$([O-]N(=O)=O)]"},
      {"[$([O][N+]=O);!H0]", -12.00f, "[$([O-][N+]=O)]"},
      {"[$([O]NC=O);!H0]", 9.40f, "[$([O-]NC=O)]"},
      {"[$([O]N=*);!H0]", 12.34f, "[$([O-]N=*)]"},
      {"[$([O]N(*)*);!H0]", 5.2f, "[$([O-]N(*)*)]"},
      {"[$([O]N);!H0]", 5.96f, "[$([O-]N)]"},
      {"[$([O]P([O-])([O-]));!H0]", 12.50f, "[$([O-]P([O-])([O-]))]"},
      {"[$([O]P([O-])=O);!H0]", 6.70f, "[$([O-]P([O-])=O)]"},
      {"[$([O]P=O);!H0]", 2.00f, "[$([O-]P=O)]"},
      {"[$([O]P[O-]);!H0]", 99.99f, "[$([O-]P[O-])]"},
      {"[$([O]Pa);!H0]", 2.10f, "[$([O-]Pa)]"},
      {"[$([O]P);!H0]", 3.08f, "[$([O-]P)]"},
      {"[$([O]S(=O)(=O)[O-]);!H0]", 2.0f, "[$([O-]S(=O)(=O)[O-])]"},
      {"[$([O]S(=O)(=O));!H0]", -99.99f, "[$([O-]S(=O)(=O))]"},
      {"[$([O]S(=O)[O-]);!H0]", 7.20f, "[$([O-]S(=O)[O-])]"},
      {"[$([O]S(=O));!H0]", 1.80f, "[$([O-]S(=O))]"},
      {"[O;!H0]", 99.99f, "[O-]"},
      {"[OH+;!H0]", -1.74f, "[O]"},
      {"[P;!H0]", 29.00f, "[P-]"},
      {"[P+;!H0]", -13.00f, "[P]"},
      {"[$([S]*=O);!H0]", 3.52f, "[$([S-]*=O)]"},
      {"[$([S]a);!H0]", 6.52f, "[$([S-]a)]"},
      {"[SH2;!H0]", 7.00f, "[SH-]"},
      {"[S;!H0]", 12.00f, "[S-]"},
      {"[SH+;!H0]", -7.00f, "[S]"},
   };

   _model.acids.clear();
   _model.basics.clear();
   _model.a_pkas.clear();
   _model.b_pkas.clear();

   for (auto i = 0; i < NELEM(simple_pka_model); i++)
   {
      BufferScanner scanner(simple_pka_model[i].acid);
      SmilesLoader loader(scanner);
      QueryMolecule &acid = _model.acids.push();
      loader.loadSMARTS(acid);
      _model.a_pkas.push(simple_pka_model[i].pka);
   }

   for (auto i = 0; i < NELEM(simple_pka_model); i++)
   {
      BufferScanner scanner(simple_pka_model[i].basic);
      SmilesLoader loader(scanner);
      QueryMolecule &basic = _model.basics.push();
      loader.loadSMARTS(basic);
      _model.b_pkas.push(simple_pka_model[i].pka);
   }

   _model.simple_model_ready = true;
}

void MoleculePkaModel::_loadAdvancedPkaModel()
{
   enum PkaType { PKA_ACID, PKA_BASIC };

   struct _PkaDef
   {
      PkaType  type;
      const char *a_fp;
      float pka;
      float deviation;
   };

   static _PkaDef advanced_pka_model[] =
   {
      {PKA_ACID, "8200022210000",  5.31, 10.19},
      {PKA_ACID, "7300021310000",  8.94, 7.84},
      {PKA_ACID, "6400020401000",  8.76, 4.51},
      {PKA_ACID, "6400020410000", 10.21, 0.00},
      {PKA_ACID, "16200022210000",  6.72, 3.77},
      {PKA_ACID, "6400020411000", 12.84, 2.80},
      {PKA_ACID, "7300021311000",  1.72, 0.55},
      {PKA_ACID, "6400020420000",  6.93, 3.75},
      {PKA_ACID, "33500020531000",  6.27, 0.00},
      {PKA_ACID, "7300021320000",  7.08, 4.58},
      {PKA_ACID, "82-10023110000",  3.06, 1.23},
      {PKA_BASIC, "7300021310000",  7.52, 7.77},
      {PKA_BASIC, "7300021320000",  7.77, 11.57},
      {PKA_BASIC, "7300021311000",  5.39, 8.91},
      {PKA_BASIC, "7300021330000",  7.84, 6.14},
      {PKA_BASIC, "82-10023110000",  4.65, 0.00},
      {PKA_BASIC, "7410020421000",  0.79, 0.00},
      {PKA_BASIC, "7410020410000",  8.86, 0.00},
      {PKA_ACID, "8200022210000|6400020421000",  4.82, 5.80},
      {PKA_ACID, "8200022210000|6400020410010",  3.70, 0.00},
      {PKA_ACID, "7300021310000|6400020410010",  1.10, 0.00},
      {PKA_ACID, "6400020401000|8200022201000", 13.27, 0.00},
      {PKA_ACID, "8200022210000|6400020411000",  3.75, 0.00},
      {PKA_ACID, "6400020410000|7410020421000", 10.21, 0.00},
      {PKA_ACID, "16200022210000|6400020421000",  4.30, 2.32},
      {PKA_ACID, "8200022210000|6400020410000", 10.33, 0.00},
      {PKA_ACID, "6400020411000|64000204400008200022201000", 10.04, 0.00},
      {PKA_ACID, "8200022210000|6400020420000", 13.56, 1.94},
      {PKA_ACID, "7300021311000|64000204110006400020411000",  2.27, 0.00},
      {PKA_ACID, "7300021311000|64000204110007300021320000",  1.17, 0.00},
      {PKA_ACID, "6400020411000|64000204100008200022201000", 13.57, 0.00},
      {PKA_ACID, "7300021310000|6400020421000", 14.05, 1.05},
      {PKA_ACID, "8200022210000|7300021320000",  8.70, 0.00},
      {PKA_ACID, "6400020420000|64000204100007410020421000",  8.46, 0.00},
      {PKA_ACID, "16200022210000|6400020420000",  9.14, 0.87},
      {PKA_ACID, "33500020531000|6400020410000640002041000082000222010008200022210000",  6.27, 0.00},
      {PKA_ACID, "8200022210000|16600020622000",  2.17, 1.57},
      {PKA_ACID, "6400020401000|6400020411000",  4.25, 0.00},
      {PKA_ACID, "8200022210000|7300021311000", 12.42, 0.00},
      {PKA_ACID, "8200022210000|6400020430000", 12.85, 1.30},
      {PKA_ACID, "7300021320000|64000204210006400020421000",  7.54, 3.65},
      {PKA_ACID, "7300021310000|16600020622000",  8.34, 1.14},
      {PKA_ACID, "7300021320000|64000204110006400020421000", 11.65, 0.00},
      {PKA_ACID, "7300021320000|64000204110006400020411000", 11.12, 0.00},
      {PKA_ACID, "82-10023110000|6400020421000",  3.06, 1.23},
      {PKA_ACID, "8200022210000|16400020421000",  1.30, 0.00},
      {PKA_ACID, "8200022210000|5300020330000",  8.83, 0.00},
      {PKA_ACID, "6400020420000|64000204210006400020421000",  6.55, 4.13},
      {PKA_ACID, "6400020411000|64000204110006400020411000", 14.90, 0.00},
      {PKA_ACID, "7300021320000|166000206220006400020421000",  5.42, 2.92},
      {PKA_ACID, "8200022210000|15500020531000",  6.30, 0.10},
      {PKA_ACID, "7300021320000|64000204210007300021330000",  3.60, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000",  9.33, 2.06},
      {PKA_BASIC, "7300021310000|6400020420000",  9.93, 4.59},
      {PKA_BASIC, "7300021320000|64000204200006400020430000", 10.12, 1.48},
      {PKA_BASIC, "7300021310000|6400020410000", 10.66, 0.00},
      {PKA_BASIC, "7300021310000|8200022220000", 12.50, 0.00},
      {PKA_BASIC, "7300021311000|6400020421000", 11.15, 6.54},
      {PKA_BASIC, "7300021320000|64000204200006400020420000", 10.27, 2.23},
      {PKA_BASIC, "7300021320000|64000204100006400020410000", 10.73, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000",  5.83, 5.69},
      {PKA_BASIC, "7300021311000|64000204110006400020411000",  5.07, 6.98},
      {PKA_BASIC, "7300021311000|64000204110008200022220000", -2.00, 0.00},
      {PKA_BASIC, "7300021311000|64000204110007300021320000",  2.49, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000",  5.34, 7.34},
      {PKA_BASIC, "7300021320000|64000204100006400020420000",  9.42, 1.22},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020410000",  9.80, 0.00},
      {PKA_BASIC, "82-10023110000|7410020440000",  4.65, 0.00},
      {PKA_BASIC, "7300021311000|64000204110007300021311000",  2.86, 0.62},
      {PKA_BASIC, "7300021320000|64000204210006400020421000",  5.05, 5.36},
      {PKA_BASIC, "7300021320000|64000204110006400020411000", -0.30, 3.50},
      {PKA_BASIC, "7300021310000|6400020440000", 10.01, 1.71},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020420000",  9.42, 1.17},
      {PKA_BASIC, "7300021320000|64000204110006400020421000",  3.95, 3.20},
      {PKA_BASIC, "7410020421000|6400020411000640002041100082-10023110000",  0.79, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020420000",  9.00, 2.16},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020421000",  5.97, 6.03},
      {PKA_BASIC, "7300021310000|6400020421000",  3.71, 6.28},
      {PKA_BASIC, "7300021311000|64000204210007300021320000",  1.60, 0.00},
      {PKA_BASIC, "7300021310000|7300021320000",  8.79, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000",  8.74, 2.18},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000",  8.30, 3.08},
      {PKA_BASIC, "7300021320000|64000204300006400020430000", 10.73, 0.33},
      {PKA_BASIC, "7300021320000|1440002044000014400020440000",  7.55, 0.00},
      {PKA_BASIC, "7300021320000|166000206220006400020421000", 11.68, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020421000",  4.26, 0.59},
      {PKA_BASIC, "7300021311000|64000204210007300021311000",  2.37, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020421000",  4.47, 0.65},
      {PKA_BASIC, "7300021330000|640002041000064000204300006400020430000",  6.75, 2.95},
      {PKA_BASIC, "7300021320000|64000204100006400020430000", 10.36, 0.63},
      {PKA_BASIC, "7300021320000|64000204210006400020430000",  9.06, 3.30},
      {PKA_BASIC, "7300021320000|64000204400006400020440000", 11.07, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020440000",  7.00, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020421000",  8.68, 3.54},
      {PKA_BASIC, "7300021311000|64000204200006400020421000",  9.58, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204400006400020440000", 11.25, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020420000",  5.20, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020430000",  8.76, 0.00},
      {PKA_BASIC, "7410020410000|6400020430000",  8.86, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210008200022210000",  5.50, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020440000",  2.00, 0.10},
      {PKA_BASIC, "7300021320000|64000204100006400020440000",  7.50, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204210006400020421000",  3.40, 0.00},
      {PKA_BASIC, "7300021311000|64000204100006400020421000",  4.80, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204210006400020421000",  1.70, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020440000",  9.67, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210007300021330000",  4.50, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210006400020430000",  8.26, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000",  8.19, 4.01},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020430000",  8.80, 0.00},
      {PKA_BASIC, "7300021320000|64000204110007300021330000",  1.70, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204300006400020430000",  6.66, 0.00},
      {PKA_ACID, "8200022210000|6400020421000|640002043000082000222010008200022210000",  2.97, 2.02},
      {PKA_ACID, "8200022210000|6400020421000|640002042000082000222010008200022210000",  3.90, 2.42},
      {PKA_ACID, "8200022210000|6400020410010|73000213000108200022210000",  3.70, 0.00},
      {PKA_ACID, "7300021310000|6400020410010|73000213000107300021310000",  1.10, 0.00},
      {PKA_ACID, "6400020401000|8200022201000|6400020401000", 13.27, 0.00},
      {PKA_ACID, "8200022210000|6400020411000|82000222010008200022210000",  3.75, 0.00},
      {PKA_ACID, "6400020410000|7410020421000|640002041000082-100231100008200022201000", 10.21, 0.00},
      {PKA_ACID, "16200022210000|6400020421000|16200022201000162000222100007300021310000",  2.95, 0.00},
      {PKA_ACID, "8200022210000|6400020410000|8200022210000", 10.33, 0.00},
      {PKA_ACID, "6400020411000|64000204400008200022201000|1710002311000017100023110000171000231100006400020411000", 10.04, 0.00},
      {PKA_ACID, "8200022210000|6400020421000|640002044000082000222010008200022210000",  2.93, 3.71},
      {PKA_ACID, "8200022210000|6400020421000|640002041100082000222010008200022210000",  4.31, 1.13},
      {PKA_ACID, "8200022210000|6400020420000|64000204400008200022210000", 12.31, 0.07},
      {PKA_ACID, "7300021311000|64000204110006400020411000|730002131100073000213110007300021320000",  2.27, 0.00},
      {PKA_ACID, "7300021311000|64000204110007300021320000|640002041100073000213110007300021311000",  1.17, 0.00},
      {PKA_ACID, "6400020411000|64000204100008200022201000|6400020411000", 13.57, 0.00},
      {PKA_ACID, "16200022210000|6400020421000|1620002221000064000204100008200022201000",  3.33, 0.00},
      {PKA_ACID, "8200022210000|6400020421000|640002041000082000222010008200022210000",  4.76, 0.00},
      {PKA_ACID, "7300021310000|6400020421000|640002041000073000213100008200022201000", 15.10, 0.00},
      {PKA_ACID, "8200022210000|7300021320000|64000204210008200022210000",  8.70, 0.00},
      {PKA_ACID, "6400020420000|64000204100007410020421000|640002042000082-100231100008200022201000",  8.46, 0.00},
      {PKA_ACID, "8200022210000|6400020420000|64000204100008200022210000", 15.50, 0.00},
      {PKA_ACID, "16200022210000|6400020420000|162000222100006400020420000",  9.00, 0.73},
      {PKA_ACID, "8200022210000|6400020420000|64000204200008200022210000", 14.60, 0.70},
      {PKA_ACID, "33500020531000|6400020410000640002041000082000222010008200022210000|33500020531000",  6.27, 0.00},
      {PKA_ACID, "8200022210000|16600020622000|6400020420000820002220100082000222010008200022210000",  1.45, 0.05},
      {PKA_ACID, "8200022210000|6400020421000|640002041001082000222010008200022210000",  2.23, 0.39},
      {PKA_ACID, "8200022210000|6400020420000|64000204100108200022210000", 13.60, 0.00},
      {PKA_ACID, "6400020401000|6400020411000|64000204010006400020421000",  4.25, 0.00},
      {PKA_ACID, "8200022210000|6400020421000|640002042100082000222010008200022210000",  3.50, 2.85},
      {PKA_ACID, "8200022210000|6400020420000|64000204110008200022210000", 15.50, 0.00},
      {PKA_ACID, "8200022210000|7300021311000|64000204210008200022210000", 12.42, 0.00},
      {PKA_ACID, "8200022210000|6400020430000|640002042000064000204200008200022210000", 14.15, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204200007300021320000820002220100073000213200008200022201000",  4.01, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204200007300021320000820002220100064000204200008200022201000",  9.62, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204210007300021320000820002220100073000213200008200022201000",  7.14, 3.25},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204300007300021320000820002220100073000213200008200022201000",  8.96, 0.00},
      {PKA_ACID, "7300021310000|16600020622000|6400020421000730002131000082000222010008200022201000",  8.34, 1.14},
      {PKA_ACID, "8200022210000|6400020430000|640002042000064000204300008200022210000", 13.90, 0.00},
      {PKA_ACID, "7300021320000|64000204110006400020421000|6400020411000730002132000064000204110008200022201000", 11.65, 0.00},
      {PKA_ACID, "8200022210000|6400020421000|640002041100064000204110008200022210000",  9.19, 2.04},
      {PKA_ACID, "7300021320000|64000204110006400020411000|640002041100073000213200006400020411000", 11.12, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204400007300021320000820002220100082000222010008200022220000",  6.13, 0.00},
      {PKA_ACID, "8200022210000|6400020430000|640002042000082000222100008200022220000", 12.61, 0.00},
      {PKA_ACID, "8200022210000|6400020430000|640002041100064000204300008200022210000", 12.22, 0.00},
      {PKA_ACID, "8200022210000|6400020430000|640002043000082000222100008200022220000", 12.11, 0.03},
      {PKA_ACID, "82-10023110000|6400020421000|640002042000082-100231100008200022201000",  2.82, 0.99},
      {PKA_ACID, "8200022210000|6400020421000|640002042100064000204210008200022210000",  6.15, 5.73},
      {PKA_ACID, "8200022210000|6400020421000|640002041100064000204210008200022210000",  8.56, 4.49},
      {PKA_ACID, "8200022210000|16400020421000|640002042100082000222010008200022210000",  1.30, 0.00},
      {PKA_ACID, "8200022210000|16600020622000|6400020421000820002220100082000222010008200022210000",  2.53, 1.83},
      {PKA_ACID, "16200022210000|6400020421000|1620002221000064000204110006400020411000",  6.62, 0.00},
      {PKA_ACID, "8200022210000|5300020330000|640002042100082000222100008200022210000",  8.83, 0.00},
      {PKA_ACID, "6400020420000|64000204210006400020421000|64000204200006400020420000820002220100064000204200008200022201000",  5.20, 0.06},
      {PKA_ACID, "6400020420000|64000204210006400020421000|64000204200008200022201000820002222000082000222010008200022220000",  5.10, 0.00},
      {PKA_ACID, "6400020420000|64000204210006400020421000|64000204100006400020420000820002220100082000222010008200022220000", 10.68, 0.00},
      {PKA_ACID, "8200022210000|6400020420000|64000204300008200022210000", 12.81, 0.90},
      {PKA_ACID, "6400020411000|64000204110006400020411000|640002041100064000204110006400020411000", 14.90, 0.00},
      {PKA_ACID, "7300021310000|6400020421000|640002042100073000213100008200022201000", 13.00, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204210007300021320000820002220100073000213300008200022201000",  7.89, 0.00},
      {PKA_ACID, "16200022210000|6400020420000|162000222100006400020421000",  9.43, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204200007300021320000820002220100073000213300008200022201000",  7.20, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204110007300021320000820002220100073000213300008200022201000",  6.70, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204400007300021320000820002220100073000213200008200022201000",  7.72, 0.29},
      {PKA_ACID, "7300021320000|166000206220006400020421000|6400020421000730002132000082000222010008200022201000162000222200007300021311000",  7.20, 0.00},
      {PKA_ACID, "8200022210000|15500020531000|8200022201000820002221000082000222100008200022220000",  6.30, 0.10},
      {PKA_ACID, "7300021320000|64000204210006400020421000|64000204400007300021320000820002220100073000213300008200022201000",  8.45, 0.00},
      {PKA_ACID, "7300021320000|166000206220006400020421000|640002042100073000213200008200022201000820002220100064000204110007300021311000",  6.70, 0.00},
      {PKA_ACID, "7300021320000|166000206220006400020421000|640002044000073000213200008200022201000820002220100064000204110006400020421000",  3.55, 1.05},
      {PKA_ACID, "7300021320000|166000206220006400020421000|640002042100073000213200008200022201000820002220100064000204210008200022220000",  5.00, 0.00},
      {PKA_ACID, "7300021320000|166000206220006400020421000|640002042100073000213200008200022201000820002220100073000213110007300021311000",  7.40, 0.00},
      {PKA_ACID, "82-10023110000|6400020421000|640002043000082-100231100008200022201000",  3.40, 0.00},
      {PKA_ACID, "7300021320000|166000206220006400020421000|640002042100073000213200008200022201000820002220100064000204210008200022201000",  4.57, 0.00},
      {PKA_ACID, "7300021320000|64000204210007300021330000|73000213200007300021320000820002220100064000204200006400020420000",  3.60, 0.00},
      {PKA_ACID, "7300021320000|64000204210006400020421000|73000213110007300021320000820002220100064000204210008200022201000",  9.69, 0.00},
      {PKA_ACID, "82-10023110000|6400020421000|640002042100082-100231100008200022201000",  3.20, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000|640002042000064000204210007300021310000",  9.21, 1.61},
      {PKA_BASIC, "7300021310000|6400020420000|64000204210007300021310000",  8.73, 1.05},
      {PKA_BASIC, "7300021310000|6400020430000|640002042100064000204300007300021310000",  9.53, 0.43},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020420000730002132000064000204200006400020421000", 10.67, 0.05},
      {PKA_BASIC, "7300021310000|6400020410000|7300021310000", 10.66, 0.00},
      {PKA_BASIC, "7300021310000|8200022220000|64000204100007300021310000", 12.50, 0.00},
      {PKA_BASIC, "7300021311000|6400020421000|730002131100073000213100007300021310000", 13.60, 0.00},
      {PKA_BASIC, "7300021310000|6400020420000|64000204100107300021310000",  5.34, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|7300021320000",  8.04, 0.00},
      {PKA_BASIC, "7300021311000|6400020421000|640002041000073000213100007300021311000", 12.10, 0.00},
      {PKA_BASIC, "7300021310000|6400020420000|64000204100007300021310000", 10.65, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020410000|7300021320000", 10.73, 0.00},
      {PKA_BASIC, "7300021310000|6400020420000|64000204200007300021310000", 10.36, 2.56},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|73000213100007300021310000730002131100073000213100007300021311000", 11.52, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110008200022220000",  0.80, 0.00},
      {PKA_BASIC, "7300021311000|64000204110008200022220000|640002041100073000213110006400020411000", -2.00, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|1620002222000073000213110006400020411000",  2.52, 0.00},
      {PKA_BASIC, "7300021311000|64000204110007300021320000|640002041100073000213110006400020411000",  2.49, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110007300021320000",  6.99, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|64000204110007300021311000162000222200007300021310000",  5.36, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|73000213100007300021311000730002131100073000213100007300021311000",  5.00, 0.00},
      {PKA_BASIC, "7300021310000|6400020420000|64000204110007300021310000",  9.49, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|64000204200007300021320000", 11.29, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020420000|73000213200006400020421000", 10.10, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000|640002041000064000204100007300021310000", 10.63, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020410000|7300021330000",  9.80, 0.00},
      {PKA_BASIC, "82-10023110000|7410020440000|64000204100006400020410000640002041000082-10023110000",  4.65, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020421000730002131100073000213200008200022201000",  3.26, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110006400020411000",  5.54, 6.51},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110007300021311000",  1.23, 0.00},
      {PKA_BASIC, "7300021311000|64000204110007300021311000|640002041100073000213110006400020411000",  2.24, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|64000204110007300021320000820002220100073000213200008200022201000",  9.45, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|73000213100007300021311000730002131100064000204110007410020421000",  0.35, 0.00},
      {PKA_BASIC, "7300021320000|64000204110006400020411000|640002041100073000213200006400020411000", -0.30, 3.50},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100073000213100007300021311000",  3.45, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002131100064000204110007300021310000",  5.71, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110007300021330000",  6.95, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|640002042100073000213200006400020421000",  9.89, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|73000213100007300021311000730002133000064000204200008200022201000",  9.20, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110007300021310000730002131100073000213100007300021311000",  6.84, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|640002042000073000213200006400020420000", 10.55, 2.05},
      {PKA_BASIC, "7300021310000|6400020440000|6400020410000640002041000064000204210007300021310000", 10.21, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020420000|73000213300006400020421000",  9.89, 0.00},
      {PKA_BASIC, "7300021311000|6400020421000|730002131000073000213110007300021330000", 14.30, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000|640002041000064000204200007300021310000", 10.63, 0.07},
      {PKA_BASIC, "7300021310000|6400020440000|6400020410000640002041000064000204100007300021310000", 10.68, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|640002041000073000213200006400020410000", 10.84, 0.00},
      {PKA_BASIC, "7300021310000|6400020440000|6400020420000640002042000064000204200007300021310000",  8.30, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002041100073000213110006400020421000",  5.19, 4.46},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|64000204110007300021311000171000231100006400020411000",  0.49, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110009100023110000", -0.44, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002132000064000204210007300021320000",  8.70, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002131100064000204210007300021320000", 10.20, 0.00},
      {PKA_BASIC, "7300021320000|64000204110006400020421000|6400020411000730002132000064000204110008200022201000",  0.75, 0.00},
      {PKA_BASIC, "7410020421000|6400020411000640002041100082-10023110000|640002041100074100204210006400020411000",  0.79, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110006400020421000",  4.86, 4.36},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110007300021310000",  6.82, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204100006400020411000",  4.81, 3.36},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020421000730002131100064000204110007300021310000",  5.77, 0.72},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110007300021320000",  3.39, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020421000730002131100064000204100007300021320000",  8.36, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020430000730002132000064000204200006400020421000",  9.66, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020420000|730002133000064000204200006400020420000",  9.20, 1.82},
      {PKA_BASIC, "7300021320000|64000204200006400020420000|640002042000073000213200006400020421000", 10.19, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020421000|730002133000073000213300008200022201000", 12.00, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000|640002042000064000204200007300021310000", 10.61, 0.03},
      {PKA_BASIC, "7300021310000|6400020440000|6400020410000640002041000064000204200007300021310000", 10.85, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020420000|73000213300006400020420000",  9.27, 1.02},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020420000|730002133000064000204100006400020410000", 10.35, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002131100064000204210007300021311000",  4.05, 0.00},
      {PKA_BASIC, "7300021310000|6400020421000|640002041100064000204110007300021310000",  3.74, 2.72},
      {PKA_BASIC, "7300021310000|6400020421000|640002041100064000204210007300021310000",  3.23, 3.48},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110006400020411000", 12.68, 0.00},
      {PKA_BASIC, "7300021311000|64000204210007300021320000|6400020411000640002042100073000213110007300021311000",  1.60, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204210007300021320000",  2.27, 0.00},
      {PKA_BASIC, "7300021320000|64000204110006400020421000|6400020411000730002132000064000204110006400020411000",  3.59, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110008200022220000",  3.28, 0.00},
      {PKA_BASIC, "7300021310000|7300021320000|64000204210007300021310000",  8.79, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020421000730002133000064000204210006400020421000", 10.70, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204100006400020411000730002131100073000213100007300021311000",  4.82, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002042000064000204100006400020420000", 10.21, 0.01},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020410000730002133000064000204200006400020420000",  9.06, 1.39},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020420000730002133000064000204200006400020421000",  8.35, 0.00},
      {PKA_BASIC, "7300021320000|64000204300006400020430000|64000204100006400020410000730002132000064000204100006400020410000", 11.05, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020410000730002133000064000204100006400020410000", 10.75, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020420000730002133000064000204200006400020420000",  8.50, 1.97},
      {PKA_BASIC, "7300021320000|1440002044000014400020440000|6400020410000640002041000064000204100007300021320000640002041000064000204100006400020410000",  7.55, 0.00},
      {PKA_BASIC, "7300021320000|166000206220006400020421000|640002042100073000213200008200022201000820002220100064000204210008200022201000", 11.68, 0.00},
      {PKA_BASIC, "7300021320000|64000204110006400020421000|7300021311000730002132000064000204110006400020421000",  6.60, 0.25},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002132000064000204110006400020421000",  5.53, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002132000064000204210007300021330000",  8.77, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020421000|730002132000064000204110006400020411000",  4.85, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204110006400020420000",  5.51, 0.38},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204100006400020421000",  7.14, 0.57},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020421000730002131100064000204100006400020411000",  6.40, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204100006400020411000730002131100064000204100006400020411000",  6.04, 1.39},
      {PKA_BASIC, "7300021311000|64000204110006400020411000|640002042100073000213110006400020421000",  6.15, 0.00},
      {PKA_BASIC, "7300021311000|64000204210007300021311000|6400020411000640002042100073000213110006400020411000",  2.37, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002131100064000204110006400020421000",  3.43, 0.00},
      {PKA_BASIC, "7300021311000|64000204110007300021311000|640002042100073000213110006400020411000",  3.47, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100064000204100007300021320000",  6.19, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|64000204110006400020411000730002132000064000204100008200022201000",  0.50, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020421000|6400020421000730002132000064000204110006400020411000",  4.39, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020421000|730002133000064000204110006400020411000",  5.36, 6.13},
      {PKA_BASIC, "7300021320000|64000204200006400020421000|6400020410000730002132000064000204110006400020411000",  5.12, 0.00},
      {PKA_BASIC, "7300021310000|6400020421000|640002042100064000204210007300021310000",  6.94, 3.05},
      {PKA_BASIC, "7300021310000|6400020420000|64000204300007300021310000",  9.70, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020411000730002131100073000213100007300021311000", 10.77, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020420000|730002133000064000204200006400020421000",  6.84, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204300006400020430000|73000213300006400020420000640002042000064000204200006400020420000",  6.75, 2.95},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020420000730002132000064000204200006400020420000", 11.06, 0.16},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020430000730002132000064000204200006400020420000", 10.30, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020430000|730002132000064000204100006400020420000", 10.99, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020421000730002131100064000204110006400020421000",  4.36, 1.67},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|64000204110006400020421000730002132000064000204110008200022201000", -0.31, 0.00},
      {PKA_BASIC, "7300021320000|64000204110006400020421000|6400020411000730002132000064000204110006400020421000",  2.23, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204210006400020421000",  4.88, 0.03},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002132000064000204210007300021311000",  8.20, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100064000204110007300021310000",  7.34, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204210007300021310000",  7.62, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100073000213200007300021320000",  4.48, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100064000204200007300021320000",  6.18, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020421000|6400020411000730002132000064000204110006400020411000",  4.17, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020430000|64000204110006400020411000730002132000064000204100006400020410000",  5.77, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020420000|73000213200006400020430000",  9.95, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|64000204110007300021320000820002220100073000213300008200022201000",  9.50, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110007300021310000730002131100073000213300008200022201000",  4.25, 0.03},
      {PKA_BASIC, "7300021310000|6400020430000|640002041000064000204300007300021310000",  9.32, 0.12},
      {PKA_BASIC, "7300021311000|6400020421000|730002131100073000213110007300021330000",  4.61, 0.00},
      {PKA_BASIC, "7300021320000|64000204400006400020440000|6400020410000640002041000064000204200007300021320000640002041000064000204100006400020420000", 11.07, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204100006400020411000730002131100064000204110006400020421000",  5.83, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002133000064000204210006400020421000",  9.12, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|7300021311000730002131100064000204210007300021310000",  3.70, 0.10},
      {PKA_BASIC, "7300021320000|64000204210006400020440000|640002041100064000204110007300021320000640002041000064000204100006400020410000",  7.00, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020421000|64000204100007300021330000640002041000064000204110006400020411000",  6.57, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020430000|730002132000064000204100006400020430000", 10.05, 0.09},
      {PKA_BASIC, "7300021311000|64000204200006400020421000|6400020420000730002131100073000213100007300021320000",  9.58, 0.00},
      {PKA_BASIC, "7300021310000|6400020430000|640002042000064000204400007300021310000", 10.17, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204400006400020440000|7300021330000640002041000064000204100006400020420000640002041000064000204100006400020420000", 11.25, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020421000|730002132000064000204110006400020421000",  3.67, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002042000064000204210008200022210000", 11.38, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020420000|730002131100073000213200006400020430000",  5.20, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020421000|64000204100007300021330000640002041000064000204110006400020421000",  7.24, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020430000730002132000064000204100006400020410000",  9.12, 0.48},
      {PKA_BASIC, "7300021311000|64000204210006400020430000|73000213100007300021311000730002132000064000204300008200022210000",  8.76, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100064000204110006400020421000",  5.48, 4.28},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|64000204110006400020411000730002132000064000204110006400020411000",  0.79, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020421000|730002133000064000204110006400020421000",  4.83, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110007300021311000730002132000073000213300008200022201000",  6.90, 0.00},
      {PKA_BASIC, "7410020410000|6400020430000|640002042000064000204210007410020410000",  8.86, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210008200022210000|64000204110006400020430000730002133000064000204210008200022201000",  5.50, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|162000222200006400020420000730002131100064000204110006400020420000",  2.10, 0.00},
      {PKA_BASIC, "7300021320000|64000204300006400020430000|64000204200006400020420000730002132000064000204200006400020420000", 10.40, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020421000730002131100064000204210007300021320000",  5.23, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020421000|6400020420000730002132000064000204100006400020421000",  4.20, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020440000|640002042100073000213110007300021320000640002041000064000204210006400020430000",  2.00, 0.10},
      {PKA_BASIC, "7300021320000|64000204100006400020440000|7300021320000640002042000064000204210006400020421000",  7.50, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204110006400020440000730002131100064000204110006400020440000",  3.58, 0.00},
      {PKA_BASIC, "7300021311000|64000204210006400020421000|64000204210007300021310000730002131100073000213100007300021311000",  6.60, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020430000|6400020420000730002132000064000204200006400020430000",  8.90, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204210006400020421000|73000213300006400020411000640002042100064000204200008200022201000",  3.40, 0.00},
      {PKA_BASIC, "7300021311000|64000204100006400020421000|730002131100064000204200007300021311000",  4.80, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002043000064000204200006400020421000",  7.35, 0.55},
      {PKA_BASIC, "7300021310000|6400020430000|640002042100064000204210007300021310000",  7.28, 0.02},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002042000064000204200006400020421000",  6.53, 0.47},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020421000|64000204200007300021330000640002042000064000204110008200022201000", 12.22, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002042000064000204200006400020430000",  9.03, 0.82},
      {PKA_BASIC, "7300021330000|640002042000064000204210006400020421000|640002043000073000213300006400020411000640002042100064000204210007300021311000",  1.70, 0.00},
      {PKA_BASIC, "7300021320000|64000204200006400020440000|64000204300007300021320000640002041000064000204100006400020410000",  9.67, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210007300021330000|6400020411000640002041100073000213300006400020430000820002220100064000204210006400020421000",  4.50, 0.00},
      {PKA_BASIC, "7300021320000|64000204100006400020420000|73000213200006400020420000",  8.20, 0.00},
      {PKA_BASIC, "7300021311000|64000204110006400020421000|6400020411000730002131100064000204200006400020421000",  6.40, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020421000|73000213100007300021311000730002132000064000204210007300021320000", 10.40, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204200006400020430000|7300021330000640002042000064000204210006400020430000",  7.80, 0.00},
      {PKA_BASIC, "7300021330000|640002042100064000204210006400020430000|6400020411000640002042100073000213300006400020420000820002220100064000204300006400020440000",  8.26, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020411000730002133000064000204200006400020420000",  7.64, 0.00},
      {PKA_BASIC, "7300021320000|64000204210006400020430000|64000204100007300021320000820002220100064000204200006400020421000", 12.36, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000|64000204200007300021330000640002044000064000204400008200022220000", 12.20, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020420000|6400020410000730002133000064000204100006400020420000",  6.56, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000|64000204100007300021330000640002044000064000204300006400020440000",  7.70, 1.82},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000|64000204200007300021330000640002043000064000204200006400020421000",  6.60, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000|64000204300007300021330000640002043000064000204200006400020440000",  9.54, 0.00},
      {PKA_BASIC, "7300021330000|640002041000064000204100006400020430000|730002133000064000204200006400020430000",  8.80, 0.00},
      {PKA_BASIC, "7300021320000|64000204110007300021330000|6400020421000730002132000064000204200006400020420000",  1.70, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204300006400020430000|640002043000073000213300006400020420000640002043000064000204200006400020430000",  6.66, 0.00},
      {PKA_BASIC, "7300021330000|640002042000064000204200006400020430000|64000204110007300021330000640002042000064000204400006400020440000",  5.40, 0.00},
   };

   _model.adv_a_pkas.clear();
   _model.adv_b_pkas.clear();

   for (auto i = 0; i < NELEM(advanced_pka_model); i++)
   {
      if (advanced_pka_model[i].type == PKA_ACID)
      {
         if (_model.adv_a_pkas.find(advanced_pka_model[i].a_fp))
            _model.adv_a_pkas.remove(advanced_pka_model[i].a_fp);

         _model.adv_a_pkas.insert(advanced_pka_model[i].a_fp);
         _model.adv_a_pkas.at(advanced_pka_model[i].a_fp).push(advanced_pka_model[i].pka);
         _model.adv_a_pkas.at(advanced_pka_model[i].a_fp).push(advanced_pka_model[i].deviation);
      }
      else if (advanced_pka_model[i].type == PKA_BASIC)
      {
         if (_model.adv_b_pkas.find(advanced_pka_model[i].a_fp))
            _model.adv_b_pkas.remove(advanced_pka_model[i].a_fp);

         _model.adv_b_pkas.insert(advanced_pka_model[i].a_fp);
         _model.adv_b_pkas.at(advanced_pka_model[i].a_fp).push(advanced_pka_model[i].pka);
         _model.adv_b_pkas.at(advanced_pka_model[i].a_fp).push(advanced_pka_model[i].deviation);
      }
   }
   _model.advanced_model_ready = true;
}

void MoleculePkaModel::_estimate_pKa_Simple (Molecule &mol, const IonizeOptions &options, Array<int> &acid_sites,
                      Array<int> &basic_sites, Array<float> &acid_pkas, Array<float> &basic_pkas)
{
//   QS_DEF(Array<int>, can_order);
//   QS_DEF(Molecule, can_mol);
   QS_DEF(Array<int>, ignore_atoms);
   QS_DEF(Array<int>, mapping);
   AromaticityOptions opts;

//   _checkCanonicalOrder(mol, can_mol, can_order);

   if (!mol.isAromatized())
   {
      mol.aromatize(opts);
   }

   MoleculeSubstructureMatcher matcher(mol);
   matcher.fmcache = new MoleculeSubstructureMatcher::FragmentMatchCache;
   matcher.use_aromaticity_matcher = true;
   ignore_atoms.clear();
   for (auto i = 0; i < _model.acids.size(); i++)
   {
      matcher.setQuery(_model.acids[i]);

      for (int j = 0; j < ignore_atoms.size(); j++)
         matcher.ignoreTargetAtom(ignore_atoms[j]);

      if (!matcher.find())
         continue;

      for (;;)
      {
         mapping.clear();
         mapping.copy(matcher.getQueryMapping(), _model.acids[i].vertexEnd());
         for (int j = 0; j < mapping.size(); j++)
         {
            if (mapping[j] > -1)
            {
               acid_sites.push(mapping[j]);
               acid_pkas.push(_model.a_pkas[i]);
               ignore_atoms.push(mapping[j]);
            }  
         }
         if (!matcher.findNext())
            break;
      }
   }

   ignore_atoms.clear();
   for (auto i = 0; i < _model.basics.size(); i++)
   {
      matcher.setQuery(_model.basics[i]);

      for (int j = 0; j < ignore_atoms.size(); j++)
         matcher.ignoreTargetAtom(ignore_atoms[j]);

      if (!matcher.find())
         continue;

      for (;;)
      {
         mapping.clear();
         mapping.copy(matcher.getQueryMapping(), _model.basics[i].vertexEnd());
         for (int j = 0; j < mapping.size(); j++)
         {
            if (mapping[j] > -1)
            {
               basic_sites.push(mapping[j]);
               basic_pkas.push(_model.b_pkas[i]);
               ignore_atoms.push(mapping[j]);
            }  
         }
         if (!matcher.findNext())
            break;
      }
   }
}

void MoleculePkaModel::_estimate_pKa_Advanced (Molecule &mol, const IonizeOptions &options, Array<int> &acid_sites,
                      Array<int> &basic_sites, Array<float> &acid_pkas, Array<float> &basic_pkas)
{
//   QS_DEF(Array<int>, can_order);
//   QS_DEF(Molecule, can_mol);
   AromaticityOptions opts;
   bool _dearomatize = false;
   int level = options.level;
   int min_level = options.min_level;

//   _checkCanonicalOrder(mol, can_mol, can_order);

   for (auto i : mol.vertices())
   {
      int a_lone = 0;
      mol.getVacantPiOrbitals(i, &a_lone);
      int a_hcnt = mol.getAtomTotalH(i);

      if (a_hcnt > 0)
      {
         float a_pka = getAcidPkaValue(mol, i, level, min_level);
         acid_sites.push(i);
         acid_pkas.push(a_pka);
//         printf("Acid site: atom index = %d, pKa = %f\n",  can_order[i], a_pka);
      }

      if (a_lone > 0)
      {
         float b_pka = getBasicPkaValue(mol, i, level, min_level);
         basic_sites.push(i);
         basic_pkas.push(b_pka);
//         printf("Basic site: atom index = %d, pKa = %f\n",  can_order[i], b_pka);
      }
   }
}

int MoleculePkaModel::_asc_cmp_cb (int &v1, int &v2, void *context)
{
   QS_DEF(Array<char>, key1);
   QS_DEF(Array<char>, key2);
   int res = 0;

   Molecule &mol = *(Molecule *)context;
   key1.clear();
   key2.clear();
   getAtomLocalKey (mol, v1, key1);
   getAtomLocalKey (mol, v2, key2);

   res = strcmp(key1.ptr(), key2.ptr());
   if (res != 0)
      return res;
   else
   {
      const Vertex &v3 = mol.getVertex(v1);
      for (auto i : v3.neighbors())
      {
          getAtomLocalKey (mol, v3.neiVertex(i), key1);;
      }

      const Vertex &v4 = mol.getVertex(v2);
      for (auto i : v4.neighbors())
      {
          getAtomLocalKey (mol, v4.neiVertex(i), key2);;
      }
      res = strcmp(key1.ptr(), key2.ptr());
   }
   return res;
}

void MoleculePkaModel::getAtomLocalFingerprint (Molecule &mol, int idx, Array<char> &fp, int level)
{
   QS_DEF(Array<int>, included_atoms);
   QS_DEF(Array<int>, dist_atoms);
   QS_DEF(Queue<int>, bfs_queue);

   QS_DEF(Array<char>, n_key);
   QS_DEF(Array<char>, bond);

   QS_DEF(Array<int>, neibs_atoms);
   QS_DEF(Array<int>, neibs_bonds);

   fp.clear();
   bfs_queue.setLength(mol.vertexEnd());
   bfs_queue.clear();
   included_atoms.clear();
   dist_atoms.clear_resize(mol.vertexEnd());
   dist_atoms.zerofill();


   n_key.clear();
   getAtomLocalKey (mol, idx, n_key);
   if (n_key.size() != 0)
      fp.appendString(n_key.ptr(), true);

   if (level == 0)
   {
      return;
   }
   else
   {
      int cur_level = 0;
      // Mark new layer after root atom
      fp.appendString("|", true);
      bfs_queue.push(idx);
      
      while (!bfs_queue.isEmpty())
      {
         int next = bfs_queue.pop();
         int dist = dist_atoms.at(next);
         if (dist == level)
            continue;
         if (dist > cur_level)
         {
            cur_level = dist;
            // Mark next new layer
            fp.appendString("|", true);
         }

         const Vertex &v = mol.getVertex(next);

         neibs_atoms.clear();
         neibs_bonds.clear();

         for (auto i : v.neighbors())
         {
           neibs_atoms.push(v.neiVertex(i));
         }
         neibs_atoms.qsort(_asc_cmp_cb, &mol);


         for (auto i = 0; i < neibs_atoms.size(); i++)
         {
            for (auto j : v.neighbors())
            {
               if (neibs_atoms[i] == v.neiVertex(j))
                  neibs_bonds.push(v.neiEdge(j));
            }
         }


//         for (auto i : v.neighbors())
         for (auto i = 0; i < neibs_atoms.size(); i++)
         {
            if (included_atoms.find(neibs_atoms[i]) == -1) 
            {
               bfs_queue.push(neibs_atoms[i]);
               included_atoms.push(neibs_atoms[i]);
               dist_atoms[neibs_atoms[i]] = dist + 1;
               bond.clear();
               ArrayOutput tmp(bond);
               n_key.clear();
               getAtomLocalKey(mol, neibs_atoms[i], n_key);
               if (n_key.size() == 0)
                  continue;
              
//               int order = mol.getBondOrder(neibs_bonds[i]);
//               tmp.printf(":%d:", order);
//               tmp.writeChar(0);
      
//               fp.appendString(bond.ptr(), true);
               fp.appendString(n_key.ptr(), true);
            }
         }
      }
      // Remove empty layer, if it was created
      if (fp[fp.size() - 2]  == '|')
         fp.remove(fp.size() - 2);
   }
   return;
}

void MoleculePkaModel::_removeExtraHydrogens(Molecule &mol)
{
   QS_DEF(Array<int>, to_remove);

   to_remove.clear();
   for (auto i : mol.vertices())
      if (mol.convertableToImplicitHydrogen(i))
         to_remove.push(i);

   if (to_remove.size() > 0)
      mol.removeAtoms(to_remove);
}

void MoleculePkaModel::_checkCanonicalOrder(Molecule &mol, Molecule &can_mol, Array<int> &order)
{
   QS_DEF(Array<int>, to_remove);
   QS_DEF(Array<int>, ignored);

   ignored.clear_resize(mol.vertexEnd());
   ignored.zerofill();
   to_remove.clear();

   for (auto i : mol.vertices())
      if (mol.convertableToImplicitHydrogen(i))
         to_remove.push(i);

   if (to_remove.size() > 0)
      mol.removeAtoms(to_remove);

   MoleculeAutomorphismSearch as;

   as.detect_invalid_cistrans_bonds = false;
   as.detect_invalid_stereocenters = false;
   as.find_canonical_ordering = true;
   as.ignored_vertices = ignored.ptr();
   as.process(mol);
   as.getCanonicalNumbering(order);
   can_mol.makeSubmolecule(mol, order, NULL);

//   printMolfile(mol);
//   printMolfile(can_mol);
}

void MoleculePkaModel::getAtomLocalKey (Molecule &mol, int idx, Array<char> &fp)
{
   QS_DEF(Array<char>, key);

   if (mol.isPseudoAtom(idx) || mol.isRSite(idx) || mol.isTemplateAtom(idx)) 
   {
      QS_DEF(Array<char>, a_desc);
      mol.getAtomDescription(idx, a_desc);
      throw Error("pKa model can't used with atom : %s", a_desc.ptr());
   }

   int a_num  = mol.getAtomNumber(idx);
   // Just bypass the hyfrogen atom
   if (a_num == ELEM_H)
      return;

   int a_val  = mol.getAtomValence(idx);
   int a_chg  = mol.getAtomCharge(idx);
   int a_rad  = mol.getAtomRadical(idx);
   int a_iso  = mol.getAtomIsotope(idx);
   int a_arom = mol.getAtomAromaticity(idx);
   int a_conn = mol.getAtomConnectivity(idx);

   int a_lone = 0;
   mol.getVacantPiOrbitals(idx, &a_lone);
   int a_hcnt = mol.getAtomTotalH(idx);

   int a_single_cnt = 0;
   int a_double_cnt = 0;
   int a_aromatic_cnt = 0;
   int a_triple_cnt = 0;
   int a_coord_cnt =0;

   const Vertex &vertex = mol.getVertex(idx);
   for (auto i : vertex.neighbors())
   {
      int order = mol.getBondOrder(vertex.neiEdge(i));

      if (order == BOND_SINGLE)
         a_single_cnt++;
      else if (order == BOND_DOUBLE)
         a_double_cnt++;
      else if (order == BOND_AROMATIC)
         a_aromatic_cnt++;
      else if (order == BOND_TRIPLE)
         a_triple_cnt++;
      else if (order == BOND_ZERO)
         a_coord_cnt++;
   }

   key.clear();
   ArrayOutput output(key);
//   output.printf("%d%d%d%d%d%d%d%d%d%d%d%d%d%d", 
//            a_num, a_val, a_chg, a_rad, a_iso, a_arom, a_lone, a_hcnt,
//            a_conn, a_single_cnt, a_double_cnt, a_aromatic_cnt, a_triple_cnt, a_coord_cnt);
   output.printf("%d%d%d%d%d%d%d%d%d%d%d%d%d", 
            a_num, a_val, a_chg, a_rad, a_iso, a_arom, a_lone, 
            a_conn, a_single_cnt, a_double_cnt, a_aromatic_cnt, a_triple_cnt, a_coord_cnt);

   output.writeChar(0);

   fp.appendString(key.ptr(), true);

   return;
}

float MoleculePkaModel::getAcidPkaValue (Molecule &mol, int idx, int level,  int min_level)
{
   QS_DEF(Array<char>, fp);
   QS_DEF(Array<int>, level_pos);
   fp.clear();
   level_pos.clear();
   float pka = 100.f;

   int a_num  = mol.getAtomNumber(idx);
   if (a_num == ELEM_H)
      return pka;

   getAtomLocalFingerprint (mol, idx, fp, level);
//   printf("Acid site: atom index = %d, fp = %s\n",  idx, fp.ptr());

   if (_model.adv_a_pkas.find(fp.ptr()))
   {  
      pka = _model.adv_a_pkas.at(fp.ptr())[0];
//      printf("Acid site found: fp = %s  level = %d pka = %4.2f, dev = %4.2f\n",  fp.ptr(), level, pka,
//             _model.adv_a_pkas.at(fp.ptr())[1]);
   }
   else
   {
      int levels = fp.count('|');
      int beg = 0;
      int end = fp.size();
      for (int i = 0; i < levels; i++)
      {
        beg = fp.find(beg + 1, end, '|');
        level_pos.push(beg);
      }

      for (int i = 0; i < level_pos.size(); i++)
      {
         if ((level_pos.size() - i - 1) < min_level)
            break;
         int next_layer = level_pos[level_pos.size() - i - 1];
         fp.remove(next_layer, fp.size() - next_layer - 1);

//         printf("Try FP = %s level = %d\n", fp.ptr(), level_pos.size() - i);

         if (_model.adv_a_pkas.find(fp.ptr()))
         {
            pka = _model.adv_a_pkas.at(fp.ptr())[0];
//            printf("Acid site found: fp = %s level = %d pka = %4.2f, dev = %4.2f\n", fp.ptr(), level_pos.size() - i, pka,
//                   _model.adv_a_pkas.at(fp.ptr())[1]);
            break;
         }
      }
   }

   return pka;
}

float MoleculePkaModel::getBasicPkaValue (Molecule &mol, int idx, int level, int min_level)
{
   QS_DEF(Array<char>, fp);
   QS_DEF(Array<int>, level_pos);
   fp.clear();
   level_pos.clear();
   float pka = -100.f;
   
   int a_num  = mol.getAtomNumber(idx);
   if (a_num == ELEM_H)
      return pka;

   getAtomLocalFingerprint (mol, idx, fp, level);
//   printf("Basic site: atom index = %d, fp = %s\n",  idx, fp.ptr());

   if (_model.adv_b_pkas.find(fp.ptr()))
   {
      pka = (_model.adv_b_pkas.at(fp.ptr())[0]);
//      printf("Basic site found: fp = %s  pka = %4.2f, dev = %4.2f\n",  fp.ptr(), pka,
//              _model.adv_b_pkas.at(fp.ptr())[1]);
   }
   else
   {
      int levels = fp.count('|');
      int beg = 0;
      int end = fp.size();
      for (int i = 0; i < levels; i++)
      {
        beg = fp.find(beg + 1, end, '|');
        level_pos.push(beg);
      }

      for (int i = 0; i < level_pos.size(); i++)
      {
         if ((level_pos.size() - i - 1) < min_level)
            break;
         int next_layer = level_pos[level_pos.size() - i - 1];
         fp.remove(next_layer, fp.size() - next_layer - 1);
         if (_model.adv_b_pkas.find(fp.ptr()))
         {
            pka = _model.adv_b_pkas.at(fp.ptr())[0];
//            printf("Basic site found: fp = %s  level = %d pka = %4.2f, dev = %4.2f\n",  fp.ptr(), level_pos.size() - i, pka,
//                   _model.adv_b_pkas.at(fp.ptr())[1]);
            break;
         }
      }
   }

   return pka;
}


IMPL_ERROR(MoleculeIonizer, "Molecule Ionizer");

CP_DEF(MoleculeIonizer);
MoleculeIonizer::MoleculeIonizer():
CP_INIT{
}

bool MoleculeIonizer::ionize (Molecule &mol, float ph, float ph_toll, const IonizeOptions &options)
{
   QS_DEF(Array<int>, acid_sites);
   QS_DEF(Array<int>, basic_sites);
   QS_DEF(Array<float>, acid_pkas);
   QS_DEF(Array<float>, basic_pkas);

   acid_sites.clear();
   basic_sites.clear();
   acid_pkas.clear();
   basic_pkas.clear();

   MoleculePkaModel::estimate_pKa(mol, options, acid_sites, basic_sites, acid_pkas, basic_pkas);

   if (acid_sites.size() > 0 || basic_sites.size() > 0)
      _setCharges(mol, ph, ph_toll, options, acid_sites, basic_sites, acid_pkas, basic_pkas);

   return true;
}

void MoleculeIonizer::_setCharges (Molecule &mol, float pH, float pH_toll, const IonizeOptions &options, Array<int> &acid_sites,
                      Array<int> &basic_sites, Array<float> &acid_pkas, Array<float> &basic_pkas)
{
   for (auto i = 0; i < acid_sites.size(); i++)
   {
      if ((acid_pkas[i] - pH) < pH_toll)
      {
         mol.setAtomCharge(acid_sites[i], mol.getAtomCharge(acid_sites[i]) - 1);
//         printf("Acid site: atom index = %d, pKa = %f\n",  acid_sites[i], acid_pkas[i]);
      }
   }

   for (auto i = 0; i < basic_sites.size(); i++)
   {
      if ((basic_pkas[i] - pH) > -pH_toll)
      {
         mol.setAtomCharge(basic_sites[i], mol.getAtomCharge(basic_sites[i]) + 1);
//         printf("Basic site: atom index = %d, pKa = %f\n",  basic_sites[i], basic_pkas[i]);
      }
   }
}