Dissecting the Energetics of Intrinsically Disordered Proteins via a Hybrid Experimental and Computational Approach.

ABSTRACT: Intrinsically disordered proteins (IDPs) play important roles in biology, but little is known about the energetics of their inter-residue interactions. Methods that have been successfully applied to analyze the energetics of globular proteins are not applicable to the fluctuating partially ordered ensembles populated by IDPs. A combined computational experimental strategy is introduced for analyzing the energetic role of individual residues in the free state of IDPs. The approach combines experimental measurements of the binding of wild-type and mutant IDPs to their partners with alchemical free energy calculations of the structured complexes. These data allow quantitative information to be deduced about the free state via a thermodynamic cycle. The approach is validated by the analysis of

SUBMITTER: Zou J 

PROVIDER: S-EPMC7291390 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature