Alignment of molecules by the Monte Carlo optimization of molecular similarity indices

✍ Scribed by Parretti, Martin F.; Kroemer, Romano T.; Rothman, Jeffrey H.; Richards, W. Graham

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 261 KB
• Volume: 18
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199708)18:11<1344::aid-jcc2>3.0.co;2-l

✦ Synopsis

3D-QSAR uses statistical techniques to correlate calculated structural properties with target properties like biological activity. The comparison of calculated structural properties is dependent upon the relative orientations of molecules in a given data set. Typically molecules are aligned by performing an overlap of common structural units. This ''alignment rule'' is adequate for a data set, that is closely related structurally, but is far more difficult to apply to either a diverse data set or on the basis of some structural property other than shape, even for sterically similar molecules. In this work we describe a new algorithm for molecular alignment based upon optimization of molecular similarity indices. We show that this Monte Carlo based algorithm is more effective and robust than other optimizers applied previously to the similarity based alignment problem. We show that QSARs derived using the alignments generated by our algorithm are superior to QSARs derived using the more common alignment of fitting of common structural units.