title: Dimerization of the p53 oligomerization domain: identification of a folding nucleus by molecular dynamics simulations.
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.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.
authors.forename: Lillian T
authors.initials: LT
authors.lastname: Chong
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Snow
authors.forename: Young Min
authors.initials: YM
authors.lastname: Rhee
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D003198:Computer Simulation; D019281:Dimerization; D008958:Models, Molecular; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D013696:Temperature; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53