GalaxyRefineComplex: Refinement of protein-protein complex model structures driven by interface repacking

Abstract

Protein-protein docking methods have been widely used to gain an atomic-level understanding of protein interactions. However, docking methods that employ low-resolution energy functions are popular because of computational efficiency. Low-resolution docking tends to generate protein complex structures that are not fully optimized. GalaxyRefineComplex takes such low-resolution docking structures and refines them to improve model accuracy in terms of both interface contact and inter-protein orientation. This refinement method allows flexibility at the protein interface and in the overall docking structure to capture conformational changes that occur upon binding. Symmetric refinement is also provided for symmetric homo-complexes. This method was validated by refining models produced by available docking programs, including ZDOCK and M-ZDOCK, and was successfully applied to CAPRI targets in a blind fashion. An example of using the refinement method with an existing docking method for ligand binding mode prediction of a drug target is also presented. A web server that implements the method is freely available at http://galaxy.seoklab.org/refinecomplex.

Template‐based modeling and ab initio refinement of protein oligomer structures using GALAXY in CAPRI round 30

“…Finally, performance of model refinement carried out by GalaxyRefineComplex at the last stage of homo‐oligomer structure prediction was analyzed. Refinement could improve models in all four accuracy measures, L‐RMSD, I‐RMSD, F nat , and F nonnat (Fig.…”

“…Therefore, a prediction method similar to that used for homo‐oligomer structure prediction was employed. The initial model, built from the templates, could be improved by GalaxyRefineComplex in all accuracy measures, with a particularly large improvement of ∼50% in F nat .…”

“…Whole oligomer structures were refined in both inter‐unit orientation and intra‐unit conformation using a flexible model refinement method GalaxyRefineComplex developed for protein complex refinement. The minimum energy structure of the refined models was selected as Model 1, and nine additional models were selected after examining the models generated from different templates and those with different loop structures after clustering with NMRclust .…”

“…Hetero‐oligomer models were built from the templates with GalaxyCassiopeia. The model structures were then refined with GalaxyRefineComplex …”

“…We used components of the GALAXY protein modeling package that detect homo‐oligomer templates (GalaxyGemini) and performed template‐based modeling (GalaxyTBM) to build template‐based models of oligomer structures. Additionally, we refined the template‐based models using GalaxyLoop to perform ab initio loop modeling, and used GalaxyRefineComplex for overall model refinement. These program components were tested in previous CASP experiments with some success .…”