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//
// Copyright (c) 2017, Guillaume GODIN
// inspired by Thomas Racek's EEM reference implementation
// All rights reserved.
//
// Redistribution and use in source and binary forms, with or without
// modification, are permitted provided that the following conditions are
// met:
//
// * Redistributions of source code must retain the above copyright
// notice, this list of conditions and the following disclaimer.
// * Redistributions in binary form must reproduce the above
// copyright notice, this list of conditions and the following
// disclaimer in the documentation and/or other materials provided
// with the distribution.
//
// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
// "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
// LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
// A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
// OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
// SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
// LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
// DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
// THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
// (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
// OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
//
// for build & set RDBASE! => export RDBASE=/Users/GVALMTGG/Github/rdkit_mine/
#include <GraphMol/RDKitBase.h>
#include "EEM.h"
#include "MolData3Ddescriptors.h"
#include <math.h>
#include <Eigen/Dense>
#include <Eigen/SVD>
using namespace Eigen;
namespace RDKit {
namespace Descriptors {
namespace {
struct EEM_arrays {
unsigned int *Atomindex;
unsigned int *EEMatomtype;
};
// Those Parameters change to adapted to the molecule dataset using the
// optimization method: The best parameters published in the NEEMP article
// (https://jcheminf.springeropen.com/articles/10.1186/s13321-016-0171-1), are
// CCD_gen_DE_RMSD_B3LYP_6311G_NPA.par from Additional file 6 was built using
// the larger dataset with B3LYP_6311G ab initio => 17769 molecules H 1, C 6, N
// 7, O 8, F 9, P 15, S 16, Cl 17, Br 35 Caution: Iodine is not in this training
// set of molecules!!!
const double kappa = 0.5125;
// 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
// 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
// 35
const double A1[] = {0.0, 2.5473, 0.0, 0.0, 0.0, 0.0, 2.7221, 2.9750,
3.1503, 2.9976, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
2.6511, 2.7026, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 2.6263};
const double A2[] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 2.7667, 2.8895, 3.0486,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 2.2933, 2.6471, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
const double A3[] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 2.6944, 3.0240, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
// 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
// 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
// 34 35
const double B1[] = {0.0, 1.1641, 0.0, 0.0, 0.0, 0.0, 0.6403, 0.9083,
1.0577, 0.9983, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.4897, 1.1537, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 1.1105};
const double B2[] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.6513, 0.6647, 0.8410,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.5759, 0.4512, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
const double B3[] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.6776, 1.4240, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0,
0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
/* simple Parameters trained using the small 500 molecules dataset.
const float kappa = 0.1960;
const float A1[] =
{0.0,2.3594,0.0,0.0,0.0,0.0,2.4541,2.5908,2.7130,0.0,0.0,0.0,0.0,0.0,0.0,0.0,2.3833};
const float A2[] =
{0.0,0.0,0.0,0.0,0.0,0.0,2.4726,2.5409,2.6766,0.0,0.0,0.0,0.0,0.0,0.0,0.0,2.4956};
const float A3[] =
{0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0};
const float B1[] =
{0.0,0.5962,0.0,0.0,0.0,0.0,0.2591,0.3316,0.5028,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.4564};
const float B2[] =
{0.0,0.0,0.0,0.0,0.0,0.0,0.2268,0.2319,0.4992,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.1493};
const float B3[] =
{0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0};
*/
// function to retreive the atomtype value based on the "highest" (e.g. max)
// bond type of an atom potential improvement : in the original publication they
// don't have access to "Aromatic type" like in RDKit
unsigned int getAtomtype(const ROMol &mol, const RDKit::Atom *atom) {
PRECONDITION(atom != nullptr, "bad atom argument")
unsigned int t = 1;
RDKit::ROMol::OEDGE_ITER beg, end;
boost::tie(beg, end) = mol.getAtomBonds(atom);
while (beg != end) {
const Bond *bond = mol[*beg];
double a = bond->getBondTypeAsDouble();
if (a == 1.5) {
a = 2.0;
}
t = std::max(t, (unsigned int)a);
++beg;
}
return t;
}
std::unique_ptr<double[]> getEEMMatrix(double *dist3D, unsigned int n,
EEM_arrays EEMatoms) {
PRECONDITION(dist3D != nullptr, "bad dist3D argument")
int sizeArray = (n + 1) * (n + 1);
double *EEM =
new double[sizeArray](); // declaration to set all elements to zeros!
/* Fill the full n * n block */
for (unsigned int i = 0; i < n; i++) {
unsigned int t = EEMatoms.EEMatomtype[i];
unsigned int idx = EEMatoms.Atomindex[i];
double v = 0.0;
if (t == 1) {
v = B1[idx];
}
if (t == 2) {
v = B2[idx];
}
if (t == 3) {
v = B3[idx];
}
EEM[i * (n + 1) + i] = v;
for (unsigned int j = i + 1; j < n; j++) {
EEM[i * (n + 1) + j] = kappa / dist3D[i * n + j];
EEM[j * (n + 1) + i] = EEM[i * (n + 1) + j];
}
}
/* Fill last column & row */
for (unsigned int i = 0; i < n; i++) {
EEM[n * (n + 1) + i] = 1.0; // column
EEM[i * (n + 1) + n] = -1.0; // row
}
return std::unique_ptr<double[]>(EEM);
}
std::unique_ptr<double[]> getBVector(const ROMol &mol, unsigned int n,
const EEM_arrays &EEMatoms) {
/* Fill vector b i.e. -A */
double *b = new double[n + 1];
for (unsigned int j = 0; j < n; j++) {
unsigned int t = EEMatoms.EEMatomtype[j];
unsigned int idx = EEMatoms.Atomindex[j];
if (t == 1) {
b[j] = -A1[idx];
}
if (t == 2) {
b[j] = -A2[idx];
}
if (t == 3) {
b[j] = -A3[idx];
}
}
b[n] = MolOps::getFormalCharge(mol); // sum of charges
return std::unique_ptr<double[]>(b);
}
EEM_arrays calculate_EEM_parameters(ROMol mol, unsigned int n) {
/* Fill vector b i.e. -A */
unsigned int *a = new unsigned int[n];
unsigned int *b = new unsigned int[n];
for (unsigned int j = 0; j < n; j++) {
b[j] = getAtomtype(mol, mol.getAtomWithIdx(j));
a[j] = mol.getAtomWithIdx(j)->getAtomicNum();
}
return EEM_arrays{a, b};
}
/* Calculate charges for a particular kappa_data structure */
void calculate_charges(ROMol mol, double *dist3D, unsigned int numAtoms,
EEM_arrays EEMatoms, std::vector<double> &res) {
std::unique_ptr<double[]> A = getEEMMatrix(dist3D, numAtoms, EEMatoms);
std::unique_ptr<double[]> b = getBVector(mol, numAtoms, EEMatoms);
MatrixXd AM = Map<MatrixXd>(A.get(), numAtoms + 1, numAtoms + 1);
VectorXd bv = Map<VectorXd>(b.get(), numAtoms + 1);
VectorXd Res(numAtoms + 1);
FullPivLU<MatrixXd> lu(AM);
Res = lu.solve(bv);
for (unsigned int aix = 0; aix < numAtoms; aix++) {
res[aix] = Res.data()[aix];
mol.getAtomWithIdx(aix)->setProp("_EEMCharge", res[aix], true);
}
}
void getEEMs(const ROMol &mol, std::vector<double> &result,
unsigned int numAtoms, int confId) {
// 3D distance matrix
double *dist3D = MolOps::get3DDistanceMat(mol, confId, false, true);
EEM_arrays EEMatoms = calculate_EEM_parameters(mol, numAtoms);
result.clear();
result.resize(numAtoms);
calculate_charges(mol, dist3D, numAtoms, EEMatoms, result);
}
} // end of anonymous namespace
void EEM(ROMol &mol, std::vector<double> &res, int confId) {
PRECONDITION(mol.getNumConformers() >= 1, "molecule has no conformers")
unsigned int numAtoms = mol.getNumAtoms();
res.clear();
res.resize(numAtoms);
// copy molecule so that we can kekulize it
RWMol wmol(mol);
// kekulize is currenlty required but it could be remove if and only if:
// we use "Aromatic type" in RDKit retrain the model without Kekulize
// that would be part of a future release if it's really important
MolOps::Kekulize(wmol, true);
getEEMs(wmol, res, numAtoms, confId);
}
} // namespace Descriptors
} // namespace RDKit
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