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PMID: 12496119 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Direct molecular dynamics observation of protein folding transition state ensemble.

Biophysical journal ·Vol. 83 ·No. 6 ·2002-12-00 ·Pages 3525-32

Ding F, Dokholyan NV, Buldyrev SV, Stanley HE, Shakhnovich EI

Abstract

The concept of the protein transition state ensemble (TSE), a collection of the conformations that have 50% probability to convert rapidly to the folded state and 50% chance to rapidly unfold, constitutes the basis of the modern interpretation of protein engineering experiments. It has been conjectured that conformations constituting the TSE in many proteins are the expanded and distorted forms of the native state built around a specific folding nucleus. This view has been supported by a number of on-lattice and off-lattice simulations. Here we report a direct observation and characterization of the TSE by molecular dynamic folding simulations of the C-Src SH3 domain, a small protein that has been extensively studied experimentally. Our analysis reveals a set of key interactions between residues, conserved by evolution, that must be formed to enter the kinetic basin of attraction of the native state.

MeSH Terms
Computer Simulation Energy Transfer Models, Molecular Protein Conformation Protein Denaturation Protein Engineering/methods Protein Folding Protein Structure, Tertiary Proto-Oncogene Proteins pp60(c-src)/chemistry Temperature src Homology Domains
Chemicals
Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ding Feng
Center for Polymer Studies, Department of Physics, Boston University, Boston, MA 02215, USA. fding@polymer.bu.edu
Dokholyan Nikolay V
Buldyrev Sergey V
Stanley H Eugene
Shakhnovich Eugene I
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(02)75352-6
Email
fding@polymer.bu.edu
Published
2002-12-00
Pages
3525-32
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1302427
Subset
IM
Grants
NIGMS NIH HHS · GM 20251 · United States
NIGMS NIH HHS · GM 52126 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(02)75352-6 PMC Full Text View journal details
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