Nucleation and the transition state of the SH3 domain
Abstract
We present a verified computational model of the SH3 domain transition state (TS) ensemble. This model was built for three separate SH3 domains using experimental s in all-atom protein folding simulations. While averaging over all conformations incorrectly considers non-TS conformations as transition states, quantifying structures as pre-TS, TS, and post-TS by measurement of their transmission coefficient (pfold, or probability to fold) allows for rigorous conclusions regarding the structure of the folding nucleus and a full mechanistic analysis of the folding process. Through analysis of the TS, we observe a highly polarized nucleus in which many residues are solvent-exposed. Mechanistic analysis suggests the hydrophobic core forms largely after an early nucleation step. SH3 presents an ideal system for studying the nucleation-condensation mechanism and highlights the synergistic relationship between experiment and simulation in the study of protein folding.
Keywords
Cite
@article{arxiv.q-bio/0503027,
title = {Nucleation and the transition state of the SH3 domain},
author = {Isaac A. Hubner and Katherine A. Edmonds and Eugene I. Shakhnovich},
journal= {arXiv preprint arXiv:q-bio/0503027},
year = {2007}
}
Comments
In press at the Journal of Molecular Biology