Development and validation of an improved algorithm for overlaying flexible molecules

作者：Taylor Robin^*; Cole Jason C; Cosgrove David A; Gardiner Eleanor J; Gillet Valerie J; Korb Oliver

来源：Journal of Computer-Aided Molecular Design, 2012, 26(4): 451-472.

DOI：10.1007/s10822-012-9573-y

• Alignment
• Overlay
• Pharmacophore

A program for overlaying multiple flexible molecules has been developed. Candidate overlays are generated by a novel fingerprint algorithm, scored on three objective functions (union volume, hydrogen-bond match, and hydrophobic match), and ranked by constrained Pareto ranking. A diverse subset of the best ranked solutions is chosen using an overlay-dissimilarity metric. If necessary, the solutions can be optimised. A multi-objective genetic algorithm can be used to find additional overlays with a given mapping of chemical features but different ligand conformations. The fingerprint algorithm may also be used to produce constrained overlays, in which user-specified chemical groups are forced to be superimposed. The program has been tested on several sets of ligands, for each of which the true overlay is known from protein-ligand crystal structures. Both objective and subjective success criteria indicate that good results are obtained on the majority of these sets.

• 出版日期2012-4