Affordable Access

Publisher Website

Dimerization of the p53 Oligomerization Domain: Identification of a Folding Nucleus by Molecular Dynamics Simulations

Authors
Journal
Journal of Molecular Biology
0022-2836
Publisher
Elsevier
Publication Date
Volume
345
Issue
4
Identifiers
DOI: 10.1016/j.jmb.2004.10.083
Keywords
  • Tumor Suppressor P53
  • Oligomerization
  • Protein Folding
  • Protein Interactions
  • Molecular Dynamics Simulation
Disciplines
  • Biology

Abstract

Dimerization of the p53 oligomerization domain involves coupled folding and binding of monomers. To examine the dimerization, we have performed molecular dynamics (MD) simulations of dimer folding from the rate-limiting transition state ensemble (TSE). Among 799 putative transition state structures that were selected from a large ensemble of high-temperature unfolding trajectories, 129 were identified as members of the TSE via calculation of a 50% transmission coefficient from at least 20 room-temperature simulations. This study is the first to examine the refolding of a protein dimer using MD simulations in explicit water, revealing a folding nucleus for dimerization. Our atomistic simulations are consistent with experiment and offer insight that was previously unobtainable.

There are no comments yet on this publication. Be the first to share your thoughts.