Systematic evaluation of predictors for binding free energy changes upon mutations in protein complexes.

ABSTRACT: The prediction of binding free energy changes ($\Delta \Delta G$) caused by mutations in protein complexes is crucial for understanding disease mechanisms and designing antibodies. Approximately 60% of pathogenic missense mutations lead to functional abnormalities by disrupting molecular interactions. However, although existing $\Delta \Delta G$ predictors exhibit strong performance in benchmarks, they suffer from inadequate generalization, a misalignment between evaluation metrics and practical needs, and poor adaptability to complex mutation scenarios. This study systematically assessed eight mainstream predictors, covering both physical energy function-based and machine learning-based methods, and constructed an independent evaluation set. This study employed multi-dimensional metrics,

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12684732 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature