Accelerating molecular docking calculations using graphics processing units

Abstract

The generation of molecular conformations and the evaluation of interaction potentials are common tasks in molecular modeling applications, particularly in protein−ligand or protein−protein docking programs. In this work, we present a GPU-accelerated approach capable of speeding up these tasks considerably. For the evaluation of interaction potentials in the context of rigid protein−protein docking, the GPU-accelerated approach reached speedup factors of up to over 50 compared to an optimized CPU-based implementation. Treating the ligand and donor groups in the protein binding site as flexible, speedup factors of up to 16 can be observed in the evaluation of protein−ligand interaction potentials. Additionally, we introduce a parallel version of our protein−ligand docking algorithm PLANTS that can take advantage of this GPU-accelerated scoring function evaluation. We compared the GPU-accelerated parallel version to the same algorithm running on the CPU and also to the highly optimized sequential CPU-based version. In terms of dependence of the ligand size and the number of rotatable bonds, speedup factors of up to 10 and 7, respectively, can be observed. Finally, a fitness landscape analysis in the context of rigid protein−protein docking was performed. Using a systematic grid-based search methodology, the GPU-accelerated version outperformed the CPU-based version with speedup factors of up to 60.