Reliable protein-protein docking with AlphaFold, Rosetta, and replica exchange.

ABSTRACT: Despite the recent breakthrough of AlphaFold (AF) in the field of protein sequence-to-structure prediction, modeling protein interfaces and predicting protein complex structures remains challenging, especially when there is a significant conformational change in one or both binding partners. Prior studies have demonstrated that AF-multimer (AFm) can predict accurate protein complexes in only up to 43% of cases (Yin et al., 2022). In this work, we combine AF as a structural template generator with a physics-based replica exchange docking algorithm to better sample conformational changes. Using a curated collection of 254 available protein targets with both unbound and bound structures, we first demonstrate that AF confidence measures (pLDDT) can be repurposed for estimating protein flexibil

SUBMITTER: Harmalkar A 

PROVIDER: S-EPMC12113263 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature