Reliable protein-protein docking with AlphaFold, Rosetta and replica-exchange
Publication type: Posted Content
Publication date: 2023-07-29
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.1In this work, we combine AlphaFold as a structural template generator with a physics-based replica exchange docking algorithm. Using a curated collection of 254 available protein targets with both unbound and bound structures, we first demonstrate that AlphaFold confidence measures can be repurposed for estimating protein flexibility and docking accuracy for multimers. We incorporate these metrics within our ReplicaDock 2.0 protocol2to complete a robust in-silico pipeline for accurate protein complex structure prediction. AlphaRED (AlphaFold-initiated Replica Exchange Docking) successfully docks failed AF predictions including 97 failure cases in Docking Benchmark Set 5.5. AlphaRED generates CAPRI acceptable-quality or better predictions for 66% of benchmark targets. Further, on a subset of antigen-antibody targets, which is challenging for AFm (19% success rate), AlphaRED demonstrates a success rate of 51%. This new strategy demonstrates the success possible by integrating deep-learning based architectures trained on evolutionary information with physics-based enhanced sampling. The pipeline is available at github.com/Graylab/AlphaRED.
Top-30
Citations by journals
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Journal of Chemical Information and Modeling
1 publication, 25%
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Russian Chemical Reviews
1 publication, 25%
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Progress in Molecular Biology and Translational Science
1 publication, 25%
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Biophysical Journal
1 publication, 25%
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Citations by publishers
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Elsevier
2 publications, 50%
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American Chemical Society (ACS)
1 publication, 25%
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Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 25%
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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