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Improved the heterodimer protein complex prediction with protein language models.

Bo Chen1, Ziwei Xie2, Jiezhong Qiu3

  • 1Department of Computer Science and Technology, Tsinghua University, Beijing, China.

Briefings in Bioinformatics
|June 16, 2023
PubMed
Summary

ESMPair, a new method using protein language models, identifies better interacting protein homologs (interologs) for complex structure prediction. This improves upon AlphaFold-Multimer, especially for low-confidence predictions and eukaryotic complexes.

Keywords:
alphafold-multimerprotein complex structure predictionprotein language model

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Area of Science:

  • Computational Biology
  • Structural Biology
  • Bioinformatics

Background:

  • Protein complex structure prediction is crucial for understanding biological functions.
  • AlphaFold-Multimer is a leading tool, but its accuracy relies on the quality of multiple sequence alignments (MSAs) from interacting homologs (interologs).

Purpose of the Study:

  • To develop a novel method, ESMPair, for identifying high-quality interologs using protein language models.
  • To enhance the accuracy of protein complex structure prediction.

Main Methods:

  • Utilized protein language models to identify interologs for protein complexes.
  • Compared ESMPair's interolog identification with AlphaFold-Multimer's default method.
  • Evaluated the impact of interolog MSA diversity on prediction accuracy.

Main Results:

  • ESMPair generated superior interologs compared to AlphaFold-Multimer's default method.
  • ESMPair significantly improved protein complex structure prediction accuracy (+10.7% DockQ).
  • Combining multiple MSA generation methods further boosted accuracy (+22% DockQ).
  • Interolog MSA diversity was identified as a key factor influencing prediction accuracy.
  • ESMPair demonstrated particular efficacy for eukaryotic complexes.

Conclusions:

  • ESMPair offers a more effective approach for identifying interologs, leading to enhanced protein complex structure prediction.
  • The diversity of interolog MSAs is critical for accurate structure prediction.
  • ESMPair shows promise for advancing structural biology, especially in eukaryotic systems.