AlphaFold and Docking Approaches for Antibody-Antigen and Other Targets: Insights From CAPRI Rounds 47-55.

Abstract

Accurate modeling of the structures of protein-protein complexes and other biomolecular interactions represents a longstanding and important challenge for computational biology. The Critical Assessment of PRedicted Interactions (CAPRI) experiment has served for over two decades as a key means to assess and compare current approaches and methods through blind predictive scenarios, highlighting useful strategies, and new developments. Here we describe the performance of our laboratory's team in recent CAPRI rounds, which included submissions for 10 modeling targets. Our team utilized a range of docking and modeling approaches, including ZDOCK, Rosetta, and ZRANK, to model, refine, and score protein-protein and protein-DNA complexes. For recent targets we utilized adaptations of AlphaFold to generate models, leading to near-native models for an antibody-peptide target, and a highly accurate (but low ranked) model for an antibody-MHC complex. These results underscore the utility of AlphaFold-based protocols for predictive protein complex modeling, including for immune recognition, and highlight considerations regarding the use of AlphaFold confidence metrics in model selection.