Integration of molecular coarse-grained model into geometric representation learning framework for protein-protein complex property prediction

Abstract

Abstract Structure-based machine learning algorithms have been utilized to predict the properties of protein-protein interaction (PPI) complexes, such as binding affinity, which is critical for understanding biological mechanisms and disease treatments. While most existing algorithms represent PPI complex graph structures at the atom-scale or residue-scale, these representations can be computationally expensive or may not sufficiently integrate finer chemical-plausible interaction details for improving predictions. Here, we introduce MCGLPPI, a geometric representation learning framework that combines graph neural networks (GNNs) with MARTINI molecular coarse-grained (CG) models to predict PPI overall properties accurately and efficiently. Extensive experiments on three types of downstream PPI property prediction tasks demonstrate that at the CG-scale, MCGLPPI achieves competitive performance compared with the counterparts at the atom- and residue-scale, but with only a third of computational resource consumption. Furthermore, CG-scale pre-training on protein domain-domain interaction structures enhances its predictive capabilities for PPI tasks. MCGLPPI offers an effective and efficient solution for PPI overall property predictions, serving as a promising tool for the large-scale analysis of biomolecular interactions.