Paper Info
Title
GalaxyDock: Protein-Ligand Docking with Flexible Protein Side-chains.
Abstract
An important issue in developing protein ligand docking methods is how to incorporate receptor flexibility. Consideration of receptor flexibility using an ensemble of precompiled receptor conformations or by employing an effectively enlarged binding pocket has been reported to be useful. However, direct consideration of receptor flexibility during energy optimization of the docked conformation has been less popular because of the large increase in computational complexity. In this paper, we present a new docking program called Galaxy Dock that accounts for the flexibility of preselected receptor side-chains by global optimization of an AutoDock-based energy function trained for flexible side-chain docking. This method was tested on 3 sets of protein-ligand complexes (HIV-PR, LXR beta, cAPK) and a diverse set of 16 proteins that involve side-chain conformational changes upon ligand binding. The cross-docking tests show that the performance of GalaxyDock is higher or comparable to previous flexible docking methods tested on the same sets, increasing the binding conformation prediction accuracy by 10%-60% compared to rigid-receptor docking. This encouraging result suggests that this powerful global energy optimization method may be further extended to incorporate larger magnitudes of receptor flexibility in the future. The program is available at http://galaxy.seoklab.org/softwares/galaxydock.html.
Year
DOI
Venue
2012
10.1021/ci300342z
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Field
DocType
Volume
Docking (dog),Searching the conformational space for docking,Ligand (biochemistry),Protein–ligand docking,Chemistry,Bioinformatics,AutoDock,Energy minimization,Side chain
Journal
52
Issue
ISSN
Citations 
12
1549-9596
14
PageRank 
References 
Authors
0.69
17
2
Name
Order
Citations
PageRank
Woong-Hee Shin1595.51
Chaok Seok216315.89