Partial peptide dissociation and binding groove plasticity in two major histocompatibility complex class I alleles - differences between alleles versus force field and sampling effects.

ABSTRACT: Major histocompatibility complex class I (MHC I) reports a cell's health status by presenting antigenic peptides inside its binding groove. However, MHC I binding grooves can differ largely in their plasticity, from binding grooves that are conformationally stable by themselves to those that require a high-affinity peptide to be bound to attain conformational stability. These latter MHC I alleles are dependent on the C-terminus of the peptide that stabilizes the F-pocket region of their binding grooves. It has remained unclear to what extent a peptide-MHC I complex (pMHC I) can tolerate the (intermittent) partial dissociation of high-affinity peptides, especially of the peptide's N-terminus. Using bias exchange umbrella sampling (BEUS), a technique to achieve enhanced sampling in molecular

SUBMITTER: Wingbermuhle S 

PROVIDER: S-EPMC9580618 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature