GalaxyDock2: Protein–ligand docking using beta‐complex and global optimization

Abstract

In this article, an enhanced version of GalaxyDock protein-ligand docking program is introduced. GalaxyDock performs conformational space annealing (CSA) global optimization to find the optimal binding pose of a ligand both in the rigid-receptor mode and the flexible-receptor mode. Binding pose prediction has been improved compared to the earlier version by the efficient generation of high-quality initial conformations for CSA using a predocking method based on a beta-complex derived from the Voronoi diagram of receptor atoms. Binding affinity prediction has also been enhanced by using the optimal combination of energy components, while taking into consideration the energy of the unbound ligand state. The new version has been tested in terms of binding mode prediction, binding affinity prediction, and virtual screening on several benchmark sets, showing improved performance over the previous version and AutoDock, on which the GalaxyDock energy function is based. GalaxyDock2 also performs better than or comparable to other state-of-the-art docking programs. GalaxyDock2 is freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

Advances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment: Meeting New Challenges

“…Group SNU docked the ligands with GalaxyDock (Shin et al, 2013) and performed manual mutagenesis-guided ligand pose selection. Group UMich-Zhang identified the binding sites by a combination of binding-specific substructure comparisons and sequence profile alignments (the so-called COACH (Yang et al, 2013b)).…”

Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues

“…Two crystal structures 4F3L (sequence identity = 28%, residues 245-361) and 3RTY (sequence identity = 18%, residues 147-339) were selected as templates. Docking was then performed by using GalaxyDock (Shin et al, 2013). A docking box on the receptor was constructed large enough to cover the important residues (R282, H285, F318, I319, H320, C327, I332, M334, A375, F398, F400) that were revealed by previous mutagenesis experiments (Goryo et al, 2007;Pandini et al, 2007).…”

“…GalaxyDock, which was used in the present study, is one of the recently developed docking methods that simultaneously consider receptor side-chain flexibility as well as ligand flexibility (Shin and Seok, 2012). This docking approach allows prediction of binding pose and binding affinity with fewer false positive results (Shin et al, 2013;Shin and Seok, 2012). Therefore, it has utility in predicting the AhR activation potency of a chemical.…”

Absolute binding free energy calculations of CBClip host–guest systems in the SAMPL5 blind challenge

“…2. First, we generated the putative binding poses of CBClip and guest molecules in two ways: (1) by slowly creating a guest molecule inside CBClip in the gas phase with a harmonic restraint to keep the guest near the center of mass of CBClip (referred to as “-MD” sets) and (2) by performing docking simulations using the GalaxyDock program (referred to as “-dock” sets), which finds the putative binding poses of protein–ligand, protein–protein and host–guest complexes via highly efficient global optimization [44–47] of the AutoDock4 scoring function [45, 48, 49]. We obtained the initial conformations for the MD simulations from scratch and did not use the conformations provided by the organizers.…”