Class FlexibleShapeAlignment


  • public class FlexibleShapeAlignment
    extends java.lang.Object
    Performs flexible Alignment of two Molecules that are prealigned. A fit molecule is thereby aligned to a rigid template. The internal degrees of freedom of the fit molecule are flexible in order to not create molecular conformations with too high strain energy, the force field potential energy is part of the objective function of the alignment optimization. The procedure is inspired by doi: 10.1021/acs.jcim.7b00618, but uses analytical gradients and optimizes the directionality overlap of pharmacophore features. Furthermore, in addition to local optimization, Monte Carlo steps are performed to randomly perturb dihedral angles of the base molecule. The first step is to perform constrained minimizations of the rigidly prealigned fit molecule. The well-depth of the positional constraint is gradually increased until to strain energy is lower than 10 kcal/mol. This yields a good initial guess of a energetically low-lying conformation of the fit molecule that still has a reasonable PheSA overlap. From this first conformation, a Monte Carlo optimization with local minimization is started. The objective function is: O = -Tphesa + lambda*Estrain*Estrain Estrain = E-E0, E0=10 kcal/mol the strain penalty is only applied if the strain energy is higher than 10 kcal/mol, otherwise the objective function is solely depending on the PheSA similarity Tphesa
    Author:
    JW