COACH-D 2.0: A Server for Template-based Modeling of Protein-ligand Interactions.

Abstract

Protein structure prediction has been transformed by AlphaFold2 and related systems; however, accurately modeling protein-ligand interactions remains a major challenge. Template-based prediction using homologous structures remains a powerful strategy. Here, we introduce COACH-D 2.0, a substantially enhanced template-based method for predicting protein-ligand binding sites. This upgrade features three key advances: (1) integration of multimeric templates from Q-BioLiP into our in-house library, (2) a new multimeric structure processing module enabling binding site prediction for protein complexes, and (3) an efficient template screening strategy that significantly boosts both prediction speed and accuracy. Evaluations against the previous version and leading methods on three benchmark datasets demonstrate the superior performance of COACH-D 2.0. The server is freely accessible at https://yanglab.qd.sdu.edu.cn/COACH-D/.