Document Detail


On the characterization and selection of diverse conformational ensembles with applications to flexible docking.
MedLine Citation:
PMID:  21233527     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
To address challenging flexible docking problems, a number of docking algorithms pregenerate large collections of candidate conformers. To remove the redundancy from such ensembles, a central problem in this context is to report a selection of conformers maximizing some geometric diversity criterion. We make three contributions to this problem. First, we resort to geometric optimization so as to report selections maximizing the molecular volume or molecular surface area (MSA) of the selection. Greedy strategies are developed, together with approximation bounds. Second, to assess the efficacy of our algorithms, we investigate two conformer ensembles corresponding to a flexible loop of four protein complexes. By focusing on the MSA of the selection, we show that our strategy matches the MSA of standard selection methods, but resorting to a number of conformers between one and two orders of magnitude smaller. This observation is qualitatively explained using the Betti numbers of the union of balls of the selection. Finally, we replace the conformer selection problem in the context of multiple-copy flexible docking. On the aforementioned systems, we show that using the loops selected by our strategy can improve the result of the docking process.
Authors:
Sébastien Loriot; Sushant Sachdeva; Karine Bastard; Chantal Prévost; Frédéric Cazals
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM     Volume:  8     ISSN:  1557-9964     ISO Abbreviation:  IEEE/ACM Trans Comput Biol Bioinform     Publication Date:    2011 Mar-Apr
Date Detail:
Created Date:  2011-01-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101196755     Medline TA:  IEEE/ACM Trans Comput Biol Bioinform     Country:  United States    
Other Details:
Languages:  eng     Pagination:  487-98     Citation Subset:  IM    
Affiliation:
INRIA Sophia-Antipolis, France.
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