Protein-protein interaction investigated by steered molecular dynamics: the TCR-pMHC complex.

ABSTRACT: We present a novel steered molecular dynamics scheme to induce the dissociation of large protein-protein complexes. We apply this scheme to study the interaction of a T cell receptor (TCR) with a major histocompatibility complex (MHC) presenting a peptide (p). Two TCR-pMHC complexes are considered, which only differ by the mutation of a single amino acid on the peptide; one is a strong agonist that produces T cell activation in vivo, while the other is an antagonist. We investigate the interaction mechanism from a large number of unbinding trajectories by analyzing van der Waals and electrostatic interactions and by computing energy changes in proteins and solvent. In addition, dissociation potentials of mean force are calculated with the Jarzynski identity, using an averaging method devel

SUBMITTER: Cuendet MA 

PROVIDER: S-EPMC2553100 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature