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//package insilico.core.descriptor.nestle;
import insilico.core.descriptor.Descriptor;
import insilico.core.descriptor.weight.QuantumNumber;
import insilico.core.molecule.InsilicoMolecule;
import org.openscience.cdk.CDKConstants;
import org.openscience.cdk.Molecule;
import org.openscience.cdk.RingSet;
import org.openscience.cdk.interfaces.IAtom;
import org.openscience.cdk.interfaces.IAtomContainer;
/**
* Custom descriptors and fixes (to be compliant with older Dragon version).
*
* @author Alberto Manganaro (a.manganaro@kode-solutions.net)
*/
public class CustomDescriptors {
public double nHM;
public double RBN;
public double Hy;
public double N_MlogP_Correction;
public CustomDescriptors(InsilicoMolecule mol) {
// Hydrophilic factor
Hy = Hy(mol);
// no. heavy atoms as in Dragon 5
nHM = 0;
// no. of rotatable bonds as in Dragon 5
RBN = 0;
// >n- correction for MLogP
N_MlogP_Correction = 0;
try {
for (IAtom CurAt : mol.GetStructure().atoms()) {
if (CurAt.getSymbol().equalsIgnoreCase("Si") ||
CurAt.getSymbol().equalsIgnoreCase("Cu") ||
CurAt.getSymbol().equalsIgnoreCase("Ag") ||
CurAt.getSymbol().equalsIgnoreCase("Cd") ||
CurAt.getSymbol().equalsIgnoreCase("Sn") ||
CurAt.getSymbol().equalsIgnoreCase("Hg") ||
CurAt.getSymbol().equalsIgnoreCase("Pb") ||
CurAt.getSymbol().equalsIgnoreCase("Bi") ||
CurAt.getSymbol().equalsIgnoreCase("As"))
nHM++;
}
} catch (Exception e) {
nHM = -999;
}
try {
double[][] ConnAugMatrix = mol.GetMatrixConnectionAugmented();
int nSK = ConnAugMatrix.length;
RingSet rings = mol.GetSSSR();
for (int i=0; i<nSK; i++)
for (int j=(i+1); j<nSK; j++) {
// only single bonds
if (ConnAugMatrix[i][j] == 1) {
// check non terminal
if (calculateVD(ConnAugMatrix, i) == 1)
continue;
if (calculateVD(ConnAugMatrix, j) == 1)
continue;
// check type of atoms
int[] numberL = QuantumNumber.getWeights(mol.GetStructure());
if ( (numberL[i] < 2) || (numberL[j] < 2))
continue;
// check amide
if (checkAmide(ConnAugMatrix, i, j))
continue;
// seems that D5 discard bonds where one atom is connected to a Cl
if ( (checkOtherConstraints(ConnAugMatrix, i)) || (checkOtherConstraints(ConnAugMatrix, j)))
continue;
// check rings
boolean inRing = false;
for (IAtomContainer curRing : rings.atomContainers())
if ( (curRing.contains(mol.GetStructure().getAtom(i))) &&
(curRing.contains(mol.GetStructure().getAtom(j))) ) {
inRing = true;
break;
}
if (inRing) continue;
RBN++;
}
}
for (int i=0; i<nSK; i++) {
// N
if (ConnAugMatrix[i][i] == 7) {
if (mol.GetStructure().getAtom(i).getFlag(CDKConstants.ISAROMATIC)) {
boolean nn = false;
int n_vd = 0;
for (int j=0; j<nSK; j++) {
if (i==j) continue;
if (ConnAugMatrix[i][j] > 0) {
n_vd++;
if (ConnAugMatrix[j][j] == 7)
if (mol.GetStructure().getAtom(j).getFlag(CDKConstants.ISAROMATIC))
nn = true;
}
}
if ( (n_vd == 3) && (!nn)) {
N_MlogP_Correction++;
}
}
}
}
} catch (Exception e) {
RBN = -999;
}
}
private int calculateVD(double[][] ConnAugMatrix, int Atom) {
int nSK = ConnAugMatrix.length;
int VD = 0;
for (int i=0; i<nSK; i++) {
if (i==Atom) continue;
if (ConnAugMatrix[Atom][i] > 0)
VD++;
}
return VD;
}
private boolean checkAmide(double[][] ConnAugMatrix, int Atom1, int Atom2) {
int nSK = ConnAugMatrix.length;
if ( ( (ConnAugMatrix[Atom1][Atom1] == 6) && (ConnAugMatrix[Atom2][Atom2] == 7) ) ||
( (ConnAugMatrix[Atom1][Atom1] == 7) && (ConnAugMatrix[Atom2][Atom2] == 6) ) ){
int Carbon = ConnAugMatrix[Atom1][Atom1] == 6 ? Atom1 : Atom2;
for (int i=0; i<nSK; i++) {
if (i==Carbon) continue;
if (ConnAugMatrix[Carbon][i] == 2)
if ( (ConnAugMatrix[i][i] == 8) || (ConnAugMatrix[i][i] == 16) )
return true;
}
}
return false;
}
private boolean checkOtherConstraints(double[][] ConnAugMatrix, int Atom) {
int nSK = ConnAugMatrix.length;
int nF=0, nCl=0, nBr=0, nI=0, VD=0;
for (int i=0; i<nSK; i++) {
if (i==Atom) continue;
if (ConnAugMatrix[Atom][i] > 0)
VD++;
// #*
if ( (ConnAugMatrix[Atom][i] == 3) )
return true;
// Cl,F,Br,I attach
if ( (ConnAugMatrix[Atom][i] == 1) && (ConnAugMatrix[i][i] == 17) )
nCl++;
if ( (ConnAugMatrix[Atom][i] == 1) && (ConnAugMatrix[i][i] == 9) )
nF++;
if ( (ConnAugMatrix[Atom][i] == 1) && (ConnAugMatrix[i][i] == 35) )
nBr++;
if ( (ConnAugMatrix[Atom][i] == 1) && (ConnAugMatrix[i][i] == 53) )
nI++;
}
if ( (VD-1) == (nCl+nF+nBr+nI)) return true;
return false;
}
private double Hy(InsilicoMolecule mol) {
try {
double[][] ConnAugMatrix = mol.GetMatrixConnectionAugmented();
Molecule CurMol = mol.GetStructure();
int nSK = CurMol.getAtomCount();
int Nhy = 0; // hydrophilic groups
int nC = 0; // number of carbons
for (int At=0; At<nSK; At++) {
int nH = CurMol.getAtom(At).getImplicitHydrogenCount();
// hydrophilic groups (-OH, -SH, -NH)
if ( (ConnAugMatrix[At][At] == 7) || (ConnAugMatrix[At][At] == 8) ||
(ConnAugMatrix[At][At] == 16) ) {
// WRONG COUNT! but consistent with Dragon 7 and 5
Nhy += nH;
// correct count of hydrophilic groups
// int nSng=0, nDbl=0, nTrp=0, nAr=0;
// for (int j=0; j<nSK; j++) {
// if (j==At) continue;
// if (ConnAugMatrix[At][j] > 0) {
// if (ConnAugMatrix[At][j] == 1) nSng++;
// if (ConnAugMatrix[At][j] == 2) nDbl++;
// if (ConnAugMatrix[At][j] == 3) nTrp++;
// if (ConnAugMatrix[At][j] == 1.5) nAr++;
// }
// }
// if ( ((nSng+nDbl+nTrp+nAr)==1) && (nSng==1) && (nH==1))
// Nhy++;
}
// nC
if ( (ConnAugMatrix[At][At] == 6) ) {
nC++;
}
}
return ( (1 + Nhy) * Log2(1 + Nhy) + nC * ( (1.0/nSK) * Log2(1.0/nSK) ) + Math.sqrt( Nhy / (nSK*nSK)) ) / Log2(1 + nSK);
} catch (Throwable e) {
return Descriptor.MISSING_VALUE;
}
}
private double Log2(double val) {
return (Math.log(val) / Math.log(2));
}
}
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