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PreprintCited by 86Protein Structure and DynamicsEnzyme Structure and FunctionMachine Learning in Bioinformatics

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Enhancing AlphaFold-Multimer-based Protein Complex Structure Prediction with MULTICOM in CASP15

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Liu, Jian, Guo, Zhiye, Wu, Tianqi, Roy, Raj S., Quadir, Farhan, Chen, Chen, Cheng, Jianlin·2023·Communications Biology
DOI 10.1101/2023.05.16.541055PMC PMC10638423

Preprint — published as 10.1038/s42003-023-05525-3 · Paper page

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Abstract

AlphaFold-Multimer has emerged as the state-of-the-art tool for predicting the quaternary structure of protein complexes (assemblies or multimers) since its release in 2021. To further enhance the AlphaFold-Multimer-based complex structure prediction, we developed a new quaternary structure prediction system (MULTICOM) to improve the input fed to AlphaFold-Multimer and evaluate and refine the outputs generated by AlphaFold2-Multimer. Specifically, MULTICOM samples diverse multiple sequence alignments (MSAs) and templates for AlphaFold-Multimer to generate structural models by using both traditional sequence alignments and new Foldseek-based structure alignments, ranks structural models through multiple complementary metrics, and refines the structural models via a Foldseek structure alignment-based refinement method. The MULTICOM system with different implementations was blindly tested in the assembly structure prediction in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 as both server and human predictors. Our server (MULTICOM_qa) ranked 3 rd among 26 CASP15 server predictors and our human predictor (MULTICOM_human) ranked 7 th among 87 CASP15 server and human predictors. The average TM-score of the first models predicted by MULTICOM_qa for CASP15 assembly targets is ∼0.76, 5.3% higher than ∼0.72 of the standard AlphaFold-Multimer. The average TM-score of the best of top 5 models predicted by MULTICOM_qa is ∼0.80, about 8% higher than ∼0.74 of the standard AlphaFold-Multimer. Moreover, the novel Foldseek Structure Alignment-based Model Generation (FSAMG) method based on AlphaFold-Multimer outperforms the widely used sequence alignment-based model generation. The source code of MULTICOM is available at: https://github.com/BioinfoMachineLearning/MULTICOM3 .

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Metadata

Authors
Liu, J., Guo, Z., Wu, T., Roy, R. S., Quadir, F., Chen, C., & Cheng, J.
Affiliations
University of Missouri (US)
Corresponding author
Cheng, Jianlin
ORCID
Venue
Communications Biology
Publisher
openRxiv
Published
2023-05-18
Volume
6
Issue
1
Pages
1140-1140
ISSN
2399-3642 (ISSN-L)
DOI
10.1101/2023.05.16.541055
PMC
PMC10638423
OpenAlex
W4388571183
Cited by
86
References
1
Citations by year
2026: 21 · 2025: 27 · 2024: 31 · 2023: 7
FWCI
7.66
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Communications Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (1763246, 2308699, 1759934)
  • U.S. Department of Energy (DESC0021303, DESC0020400)
  • U.S. Department of Health and Human Services (R01GM093123 and R01GM146340)
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM093123, R01GM146340)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
Keywords
protein complex structure prediction, quaternary structure prediction, AlphaFold-Multimer, multiple sequence alignment, CASP15, TM-score

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