Boosting AlphaFold protein tertiary structure prediction through MSA engineering and extensive model sampling and ranking in CASP16.

ABSTRACT: AlphaFold2 and AlphaFold3 have revolutionized protein structure prediction by enabling high-accuracy structure predictions for most single-chain proteins. However, obtaining high-quality predictions for difficult targets with shallow or noisy multiple sequence alignments and complicated multi-domain architectures remains challenging. We present MULTICOM4, an integrative structure prediction system that uses diverse MSA generation, large-scale model sampling, and an ensemble model quality assessment strategy to improve model generation and ranking of AlphaFold2 and AlphaFold3. In the 16th Critical Assessment of Techniques for Protein Structure Prediction, our predictors built on MULTICOM4 ranked among the top out of 120 predictors in tertiary structure prediction and outperformed a standard

SUBMITTER: Liu J 

PROVIDER: S-EPMC12623963 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature