Thermodynamics and folding kinetics analysis of the SH3 domain from discrete molecular dynamics

Jose M. Borreguero, Nikolay V. Dokholyan, Sergey V. Buldyrev, Eugene I. Shakhnovich, H. Eugene Stanley

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

We perform a detailed analysis of the thermodynamics and folding kinetics of the SH3 domain fold with discrete molecular dynamic simulations. We propose a protein model that reproduces some of the experimentally observed thermodynamic and folding kinetic properties of proteins. Specifically, we use our model to study the transition state ensemble of the SH3 fold family of proteins, a set of unstable conformations that fold to the protein native state with probability 1/2. We analyze the participation of each secondary structure element formed at the transition state ensemble. We also identify the folding nucleus of the SH3 fold and test extensively its importance for folding kinetics. We predict that a set of amino acid contacts between the RT-loop and the distal hairpin are the critical folding nucleus of the SH3 fold and propose a hypothesis that explains this result.

Original languageEnglish (US)
Pages (from-to)863-876
Number of pages14
JournalJournal of Molecular Biology
Volume318
Issue number3
DOIs
StatePublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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