AlphaCRV: A Pipeline for Identifying Accurate Binder Topologies in Mass-Modeling with AlphaFold

Abstract The speed and accuracy of deep learning-based structure prediction algorithms makes it now possible to perform in silico “pull-downs” to identify protein-protein interactions at a proteome-wide scale. However, existing scoring algorithms struggle to accurately identify correct interactions at such a large scale, resulting in an excessive number of false positives. Here, we introduce AlphaCRV, a Python package that helps identify correct interactors in a one-against-many AlphaFold screen by clustering, ranking, and visualizing conserved binding topologies, based on protein sequence and fold. Competing Interest Statement The authors have declared no competing interest. Footnotes Availability and implementation: AlphaCRV is a Python package for Linux, freely available at https://github.com/strubelab/AlphaCRV