Predictive QM/MM Modeling of Modulations in Protein-Protein Binding by Lysine Methylation.

ABSTRACT: Lysine methylation is a key regulator of protein-protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein-protein binding free energies are sensitive to the extent of methylation. These sensitivities have been rationalized in terms of chemical and structural features present in the binding pockets of methyllysine binding domains. However, understanding their specific roles requires an energetic analysis. Here we propose a theoretical framework to combine quantum and molecular mechanics methods, and compute the effect of methylation on protein-protein binding free energies. The advantages of this approach are that it derives contributions from all local non-trivial effects of methylation on induction, polarizability and dispersion di

SUBMITTER: Rahman S 

PROVIDER: S-EPMC9801414 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature