com.actelion.research.chem.phesaflex.EvaluableFlexibleOverlap Maven / Gradle / Ivy

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package com.actelion.research.chem.phesaflex;


import java.util.Arrays;
import java.util.Map;

import com.actelion.research.chem.StereoMolecule;
import com.actelion.research.chem.forcefield.mmff.ForceFieldMMFF94;
import com.actelion.research.chem.optimization.Evaluable;
import com.actelion.research.chem.phesa.AtomicGaussian;
import com.actelion.research.chem.phesa.Gaussian3D;
import com.actelion.research.chem.phesa.MolecularVolume;
import com.actelion.research.chem.phesa.QuickMathCalculator;
import com.actelion.research.chem.phesa.VolumeGaussian;
import com.actelion.research.chem.phesa.PheSAAlignment;
import com.actelion.research.chem.phesa.pharmacophore.PPGaussian;



/**
 * @author JW, Oktober 2019
 * functionality for optimizing PheSA overlap (Pharmacophore+Shape) allowing for molecular flexibility
 */


public class EvaluableFlexibleOverlap implements Evaluable  {

	//private static final double SCALE = -250;
	//private static final double DELTA = -0.01;
	private static final double LAMBDA = 0.0625;
	private double e0 = 0.0;
	private StereoMolecule fitMol;
	private PheSAAlignment shapeAlign;
	private boolean[] isHydrogen;
	private double[] v; //coordinates of the atoms
	private double[][] precalcPow;
	private double[] precalcExp;
    private double oAA;
    private double oAApp;
    private ForceFieldMMFF94 ff;
    private Map ffOptions;
    private double ppWeight;
    
	public EvaluableFlexibleOverlap(PheSAAlignment shapeAlign, StereoMolecule refMol, StereoMolecule fitMol, double ppWeight, boolean[] isHydrogen,double[] v, Map ffOptions) {
		ForceFieldMMFF94.initialize(ForceFieldMMFF94.MMFF94SPLUS);
		this.ffOptions = ffOptions;
		ff = new ForceFieldMMFF94(fitMol, ForceFieldMMFF94.MMFF94SPLUS, this.ffOptions);
		this.shapeAlign = shapeAlign;
		this.fitMol = fitMol;
		this.isHydrogen = isHydrogen;
		this.ppWeight = ppWeight;
		this.v = v;
		for(int i=0;i0.0) {
						totalOverlap += atomOverlap;
						gradientPrefactor = atomOverlap*-2*refAt.getWidth()*fitAt.getWidth()/(refAt.getWidth()+fitAt.getWidth());
					}

				}
				grad[3*a] += (2*xj-2*xi)*gradientPrefactor;
				grad[3*a+1] += (2*yj-2*yi)*gradientPrefactor;
				grad[3*a+2] += (2*zj-2*zi)*gradientPrefactor;
				}

		
		}
		
		for(VolumeGaussian refVG:refMolGauss.getVolumeGaussians()){
			double xi = refVG.getCenter().x;
			double yi = refVG.getCenter().y;
			double zi = refVG.getCenter().z;
			for(AtomicGaussian fitAt:molGauss.getAtomicGaussians()){
				int a = fitAt.getAtomId();
				double atomOverlap = 0.0;
				double xj = v[3*a];
				double yj = v[3*a+1];
				double zj = v[3*a+2];
				double dx = xi-xj;
				double dy = yi-yj;
				double dz = zi-zj;
				double Rij2 = dx*dx + dy*dy + dz*dz;
				double alphaSum = refVG.getWidth() + fitAt.getWidth();
				double gradientPrefactor=0.0;
				if(Rij20.0) {
						totalOverlap += atomOverlap;
						gradientPrefactor = atomOverlap*-2*refVG.getWidth()*fitAt.getWidth()/(refVG.getWidth()+fitAt.getWidth());
					}

				}
				grad[3*a] += (2*xj-2*xi)*gradientPrefactor;
				grad[3*a+1] += (2*yj-2*yi)*gradientPrefactor;
				grad[3*a+2] += (2*zj-2*zi)*gradientPrefactor;
				}

		
		}


		return totalOverlap; 
	
	}
	
	public double getFGValuePP(double[] grad) {
		
		MolecularVolume molGauss = shapeAlign.getMolGauss();

		MolecularVolume refMolGauss = shapeAlign.getRefMolGauss();

		for(int i=0;i0.0) {
						double sim = refPP.getSimilarity(fitPP);
						atomOverlap *= sim;
						totalOverlap += atomOverlap;
						gradientPrefactor = atomOverlap*-2*refPP.getWidth()*fitPP.getWidth()/(refPP.getWidth()+fitPP.getWidth());
						grad[3*a] += (2*xj-2*xi)*gradientPrefactor*sim;
						grad[3*a+1] += (2*yj-2*yi)*gradientPrefactor*sim;
						grad[3*a+2] += (2*zj-2*zi)*gradientPrefactor*sim;
						fitPP.getPharmacophorePoint().getDirectionalityDerivativeCartesian(grad, v, fitPP.getPharmacophorePoint().getDirectionality(), sim);					}

				}

				}

		
		}

		return totalOverlap; 
	
	}
	
	public double getFGValueShapeSelf(double[] grad, MolecularVolume molGauss,boolean rigid) {
		
		for(int i=0;i0.0) {
				gradientPrefactor = atomOverlap*-2*refAt.getWidth()*fitAt.getWidth()/(refAt.getWidth()+fitAt.getWidth());
			}

		}
			grad[3*b] += (2*xj-2*xi)*gradientPrefactor;
			grad[3*b+1] += (2*yj-2*yi)*gradientPrefactor;
			grad[3*b+2] += (2*zj-2*zi)*gradientPrefactor;
			
			return atomOverlap;
		}
	

	
	
	public double getFGValueSelfPP(double[] grad, MolecularVolume molVol,boolean rigid) {
		double xi,yi,zi,xj,yj,zj;
		
		for(int i=0;i0.0) {
						double sim = refPP.getSimilarity(fitPP);
						atomOverlap *= sim;
						totalOverlap += atomOverlap;
						gradientPrefactor = atomOverlap*-2*refPP.getWidth()*fitPP.getWidth()/(refPP.getWidth()+fitPP.getWidth());
						grad[3*a] += (2*xj-2*xi)*gradientPrefactor*sim;
						grad[3*a+1] += (2*yj-2*yi)*gradientPrefactor*sim;
						grad[3*a+2] += (2*zj-2*zi)*gradientPrefactor*sim;
						fitPP.getPharmacophorePoint().getDirectionalityDerivativeCartesian(grad, v, fitPP.getPharmacophorePoint().getDirectionality(), sim);					}

				}

				}
			
		}


		return totalOverlap; 
		
	
	}
	
	

	@Override
	public EvaluableFlexibleOverlap clone() {
		return new EvaluableFlexibleOverlap(this);
	}
		
}