Markov state modeling reveals alternative unbinding pathways for peptide-MHC complexes.

ABSTRACT: Peptide binding to major histocompatibility complexes (MHCs) is a central component of the immune system, and understanding the mechanism behind stable peptide-MHC binding will aid the development of immunotherapies. While MHC binding is mostly influenced by the identity of the so-called anchor positions of the peptide, secondary interactions from nonanchor positions are known to play a role in complex stability. However, current MHC-binding prediction methods lack an analysis of the major conformational states and might underestimate the impact of secondary interactions. In this work, we present an atomically detailed analysis of peptide-MHC binding that can reveal the contributions of any interaction toward stability. We propose a simulation framework that uses both umbrella sampling and

SUBMITTER: Abella JR 

PROVIDER: S-EPMC7720115 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature