title: Development and validation of an improved algorithm for overlaying flexible molecules.
abstract: 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.
authors.affiliation: Taylor Cheminformatics Software, 54 Sherfield Avenue, Rickmansworth, Hertfordshire, WD3 1NL, UK. robin@justmagnolia.co.uk
authors.forename: Robin
authors.initials: R
authors.lastname: Taylor
authors.forename: Jason C
authors.initials: JC
authors.lastname: Cole
authors.forename: David A
authors.initials: DA
authors.lastname: Cosgrove
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Gardiner
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Gillet
authors.forename: Oliver
authors.initials: O
authors.lastname: Korb
mesh_terms: D000465:Algorithms; D015394:Molecular Structure