com.actelion.research.chem.conf.MolecularFlexibilityCalculator Maven / Gradle / Ivy

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There is a newer version: 2024.12.1
package com.actelion.research.chem.conf;

import com.actelion.research.chem.Molecule;
import com.actelion.research.chem.StereoMolecule;

public class MolecularFlexibilityCalculator {
	public MolecularFlexibilityCalculator() {
		TorsionDB.initialize(TorsionDB.MODE_ANGLES);
		}

	/**
	 * Calculates a molecular flexibility as a value from 0.0 to 1.0 considering torsion statistics
	 * derived from the CSD database (torsion maxima, frequencies, and 50% intervals) of rotatable bonds.
	 * It also considers the effect that a specific torsion has on the overall geometry of the
	 * molecule, i.e. central bonds are weighted higher than those in the periphery.
	 * Currently it is assumed that the mol consists of one(!!!) fragment only.
	 * 


	 * In more detail the following steps are done:

	 * -- relevant rotatable bonds are determined, i.e. single bonds, which are not in a ring with less than 6 members,
	 *   where both atoms are sp2 or sp3 and carry at least one more non-hydrogen neighbor,
	 *   which are not symmetrically redundant, and those where a torsion change modifies the relative location of atoms.
	 *   For chains of conjugated triple bonds the following applies:
	 *   If at least one terminal sp2/sp3 atom has no external neighbor, then no single bond is considered rotatable.
	 *   Otherwise that terminal single bond connecting the smaller substituent is considered the only rotatable bond
	 *   of the linear atom strand.

	 * -- the local environment of any rotatable bonds is characterized by its first and second shell of neighbours plus
	 *   various properties as ring membership, aromaticity, stereo configuration, if applicable, etc.

	 * -- a bond specific flexibility value is calculated from the torsion angle histogram of equivalent bonds
	 *   within any high-resolution x-ray structures of the CSD database. (in the rare cases with no CSD precedents
	 *   the histogram is roughly predicted). Frequency distributions with wide and multiple distribution maxima of
	 *   similar heights receive the local flexibility values around close to 1.0 while histograms with one narrow single
	 *   peak are close to 0.0.

	 * -- a weighting factor is assigned to every rotatable bond as follows:

	 *   - for ring bonds: factor=0.33, since ring bonds cannot be changed without affecting typically two other rings bonds

	 *   - other bonds: factor=sqrt(2.0 * smallerSideNonHydrogenAtomCount / moleculeNonHydrogenAtomCount)

	 * -- from the number of all bonds, rotatabale bonds, their specific flexibility values and weighting factor an
	 *   overall flexibility value is calculated with a non-linear incremental approach.

	 * @param mol one molecular fragment(!)
	 * @return
	 */
	public float calculateMolecularFlexibility(StereoMolecule mol) {
		mol.ensureHelperArrays(Molecule.cHelperRings);
		if (mol.getAtoms() == 0)
			return 0f;

		boolean[] isRotatableBond = new boolean[mol.getBonds()];
		int rotatableBondCount = TorsionDB.findRotatableBonds(mol, false, isRotatableBond);
		if (rotatableBondCount == 0)
			return 0f;

		// calculate flexibility values of individual rotatable bonds
		float[] bondFlexibility = new float[mol.getBonds()];
		for (int bond=0; bond