Work

FTFlex: accounting for binding site flexibility to improve fragment-based identification of druggable hot spots

Year: 2013

Type: article

Abstract: UNLABELLED: Computational solvent mapping finds binding hot spots, determines their druggability and provides information for drug design. While mapping of a ligand-bound structure yields more accurate results, usually the apo structure serves as the starting point in design. The FTFlex algorithm, implemented as a server, can modify an apo structure to yield mapping results that are similar to those of the respective bound structure. Thus, FTFlex is an extension of our FTMap server, which only considers rigid structures. FTFlex identifies flexible residues within the binding site and determines alternative conformations using a rotamer library. In cases where the mapping results of the apo structure were in poor agreement with those of the bound structure, FTFlex was able to yield a modified apo structure, which lead to improved FTMap results. In cases where the mapping results of the apo and bound structures were in good agreement, no new structure was predicted. AVAILABILITY: FTFlex is freely available as a web-based server at http://ftflex.bu.edu/.

Source: Bioinformatics

DOI: 10.1093/bioinformatics/btt102

Authors: Laurie E. Grove, David R. Hall, Dmitri Beglov, Sandor Vajda, Dima Kozakov

Institutions: Boston University, Wentworth Institute of Technology

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: bronze

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: High-throughput portable software for fragment-based drug design, A multistage approach to protein-protein docking, Computational mapping of proteins for the binding of ligands, G700947639