Exploring Protein-Protein Interactions with MEGADOCK: Parallelization, Application, and Open Database

Overview

Abstract

Protein-protein interaction (PPI) plays a core role in cellular functions. In recent years, PPI prediction methods based on protein docking have been developed and have been applied for large-scale PPI network prediction based on tertiary structures. We have developed an ultra-high-throughput PPI prediction system based on rigid-body protein-protein docking and supercomputing, named MEGADOCK[1, 2]. MEGADOCK can perform faster docking based on its improved scoring function and implementation for heterogeneous supercomputers[2, 4-6]. MEGADOCK achieved excellent scalability on supercomputing environments, such as K computer and TSUBAME, and realized genome-wide scale PPI network prediction. We applied the MEGADOCK system to a number of interactome analyses; (a) bacterial chemotaxis, (b) human apoptosis, (c) human EGFR signaling, and (d) RNA decay at the early cellular reprogramming stage. In addition, we have constructed an integrated database of PPI predictions named MEGADOCK-Web to accelerate PPI researches. MEGADOCK-Web provides the four functions, 1) Searching PPI predictions from 28,331,628 prediction results, 2) displaying known PPI, 3) visualizing candidate of interaction with query protein on a biochemical pathway, and 4) visualizing predicted complex structure by a 3D molecular viewer.