Deconvolving mutation effects on protein stability and function with disentangled protein language models.

ABSTRACT: Understanding how evolutionary constraints shape protein sequences is fundamental to deciphering the molecular mechanisms underlying protein stability and function, which has broad implications in protein engineering and therapeutics development. Recent advances in protein language models (pLMs) have enabled accurate prediction of mutation effects through evolutionary information, effectively capturing the selective pressure that governs protein sequence variation. A critical challenge, however, remains in disentangling the intertwined mutation effects on protein stability and function, as evolutionary signals conflate both stability-driven and function-driven pressures, obscuring the mechanistic basis of mutation effects and limiting their utility for rational protein engineering. In this

SUBMITTER: Ding K 

PROVIDER: S-EPMC12889624 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature