Energy-based Graph Convolutional Networks for Scoring Protein Docking Models

TL;DR

This paper introduces energy-based graph convolutional networks that leverage 3D protein structure graphs to improve scoring and quality assessment of protein docking models, achieving significant performance gains.

Contribution

It presents the first successful application of graph convolutional networks to protein docking, integrating energy prediction and quality assessment in a unified framework.

Findings

Significantly improved model ranking on CAPRI test set.

Comparable performance on diverse docking protocols.

About 27% improvement in quality assessment over previous methods.

Abstract

Structural information about protein-protein interactions, often missing at the interactome scale, is important for mechanistic understanding of cells and rational discovery of therapeutics. Protein docking provides a computational alternative to predict such information. However, ranking near-native docked models high among a large number of candidates, often known as the scoring problem, remains a critical challenge. Moreover, estimating model quality, also known as the quality assessment problem, is rarely addressed in protein docking. In this study the two challenging problems in protein docking are regarded as relative and absolute scoring, respectively, and addressed in one physics-inspired deep learning framework. We represent proteins' and encounter complexes' 3D structures as intra- and inter-molecular residue contact graphs with atom-resolution node and edge features. And we propose a novel graph convolutional kernel that pool interacting nodes' features through edge features so that generalized interaction energies can be learned directly from graph data. The resulting energy-based graph convolutional networks (EGCN) with multi-head attention are trained to predict intra- and inter-molecular energies, binding affinities, and quality measures (interface RMSD) for encounter complexes. Compared to a state-of-the-art scoring function for model ranking, EGCN has significantly improved ranking for a CAPRI test set involving homology docking; and is comparable for Score_set, a CAPRI benchmark set generated by diverse community-wide docking protocols not known to training data. For Score_set quality assessment, EGCN shows about 27% improvement to our previous efforts. Directly learning from 3D structure data in graph representation, EGCN represents the first successful development of graph convolutional networks for protein docking.