Q-Dock(LHM): Low-resolution refinement for ligand comparative modeling

TitleQ-Dock(LHM): Low-resolution refinement for ligand comparative modeling
Publication TypeJournal Article
Year of Publication2010
AuthorsBrylinski M, Skolnick J
JournalJ Comput Chem
Volume31
Issue5
Pagination1093-105
Date Published2010 Apr 15
ISSN1096-987X
KeywordsBinding Sites, Ligands, Models, Biological, Protein Binding, Proteins
Abstract

The success of ligand docking calculations typically depends on the quality of the receptor structure. Given improvements in protein structure prediction approaches, approximate protein models now can be routinely obtained for the majority of gene products in a given proteome. Structure-based virtual screening of large combinatorial libraries of lead candidates against theoretically modeled receptor structures requires fast and reliable docking techniques capable of dealing with structural inaccuracies in protein models. Here, we present Q-Dock(LHM), a method for low-resolution refinement of binding poses provided by FINDSITE(LHM), a ligand homology modeling approach. We compare its performance to that of classical ligand docking approaches in ligand docking against a representative set of experimental (both holo and apo) as well as theoretically modeled receptor structures. Docking benchmarks reveal that unlike all-atom docking, Q-Dock(LHM) exhibits the desired tolerance to the receptor's structure deformation. Our results suggest that the use of an evolution-based approach to ligand homology modeling followed by fast low-resolution refinement is capable of achieving satisfactory performance in ligand-binding pose prediction with promising applicability to proteome-scale applications.

Alternate JournalJournal of Computational Chemistry
Full Text

iPaper

PreviewAttachmentSize
2010_jcc.pdf559.64 KB

© Michal Brylinski
This website is hosted at the CCT