Dimerization of the p53 oligomerization domain: identification of a folding nucleus by molecular dynamics simulations.
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.
Chong
Lillian T
LT
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.
Snow
Christopher D
CD
Rhee
Young Min
YM
Pande
Vijay S
VS
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*
D016159:Tumor Suppressor Protein p53