CHDOCK: a hierarchical docking approach for modeling Cn symmetric homo-oligomeric complexes

Abstract

Protein–protein interactions are crucial in many biological processes. Therefore, determining the complex structure between proteins is valuable for understanding the molecular mechanism and developing drugs. Many proteins like ion channels are formed by symmetric homo-oligomers. In this study, we have proposed a hierarchical docking algorithm to predict the structure of Cn symmetric protein complexes, which is referred to as CHDOCK. The symmetric binding modes were first constructed by an FFT-based docking algorithm and then optimized by our iterative scoring function for protein–protein interactions. When tested on a symmetric protein docking benchmark of 212 homo-oligomeric complexes with Cn symmetry, CHDOCK obtained a significantly better performance in binding mode predictions than three state-of-the-art symmetric docking methods, M-ZDOCK, SAM, and SymmDock. When the top 10 predictions were considered, CHDOCK achieved a success rate of 44.81% and 72.17% for unbound docking and bound docking, respectively in comparison to those of 36.79% and 65.09% for M-ZDOCK, 31.60% and 54.25% for SAM, and 30.66% and 31.60% for SymmDock. CHDOCK is computationally efficient and can normally complete a symmetric docking calculation within 30 min. The CHDOCK can be freely accessed by a web server at http://huanglab.phys.hust.edu.cn/hsymdock/.