actifpTM: a refined confidence metric of AlphaFold2 predictions involving flexible regions.

Abstract

One of the main advantages of deep learning models of protein structure, such as Alphafold2, is their ability to accurately estimate the confidence of a generated structural model, which allows us to focus on highly confident predictions. The ipTM score provides a confidence estimate of interchain contacts in protein-protein interactions. However, interactions, in particular motif-mediated interactions, often also contain regions that remain flexible upon binding. These noninteracting flanking regions are assigned low confidence values and will affect ipTM, as it considers all interchain residue-residue pairs, and two models of the same motif-domain interaction, but differing in the length of their flanking regions, would be assigned very different values. Here, we propose actual interface pTM (actifpTM), a modified ipTM measure, that focuses on the residues participating in the interaction, resulting in a more robust measure of interaction confidence. Besides, actifpTM is calculated both for the full complex as well as for each pair of chains, making it well-suited for evaluating multi-chain complexes with a particularly critical binding interface, such as antibody-antigen interactions. The method is available as part of the ColabFold (https://github.com/sokrypton/ColabFold) repository, installable both locally or usable with Colab notebook.