QUASI: a novel method for simultaneous superposition of multiple flexible ligands and virtual screening using partial similarity

N.P. Todorov, I.L. Alberts, I.J.P. de Esch, P.M. Dean

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The structure of many receptors is unknown, and only information about diverse ligands binding to them is available. A new method is presented for the superposition of such ligands, derivation of putative receptor site models and utilization of the models for screening of compound databases. In order to generate a receptor model, the similarity of all ligands is optimized simultaneously taking into account conformational flexibility and also the possibility that the ligands can bind to different regions of the site and only partially overlap. Ligand similarity is defined with respect to a receptor site model serving as a common reference frame. The receptor model is dynamic and coevolves with the ligand alignment until an optimal self-consistent superposition is achieved. When ligand conformational flexibility is permitted, different superposition models are possible and consistent with the data. Clustering of the superposition solutions is used to obtain diverse models. When the models are used to screen a database of compounds, high enrichments are obtained, comparable to those obtained in docking studies. © 2007 American Chemical Society.
Original languageEnglish
Pages (from-to)1007-20
JournalJournal of Chemical Information and Modeling
Volume47
Issue number3
DOIs
Publication statusPublished - 2007

Fingerprint

Dive into the research topics of 'QUASI: a novel method for simultaneous superposition of multiple flexible ligands and virtual screening using partial similarity'. Together they form a unique fingerprint.

Cite this