Accurate predictions of protein mutational effects accelerated with a hybrid-topology free energy protocol.

ABSTRACT: Quantifying the effects of point mutations is of utmost interest for pharmaceutical and biotechnological applications. Reliable computational methods range from statistical and AI-based to physics-based approaches, with the optimal balance between accurate and fast predictions remaining a challenge. Free energy perturbation (FEP) simulations, a powerful physics-based approach available for decades, constitutes nowadays a method of common application in protein mutational studies. We present QresFEP-2, a novel hybrid-topology FEP protocol benchmarked on a comprehensive protein stability dataset of 10 protein systems, encompassing almost 600 mutations. QresFEP-2 combines excellent accuracy with the highest computational efficiency among available FEP protocols, and its robustness is further

SUBMITTER: Koenekoop L 

PROVIDER: S-EPMC12634679 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature