title: Thermodynamics and folding kinetics analysis of the SH3 domain form discrete molecular dynamics.
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.
authors.affiliation: Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA. jmborr@bu.edu
authors.forename: Jose M
authors.initials: JM
authors.lastname: Borreguero
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Buldyrev
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Shakhnovich
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Stanley
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents; D007700:Kinetics; D008958:Models, Molecular; D017510:Protein Folding; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D050737:Proto-Oncogene Proteins c-crk; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D003432:Cross-Linking Reagents; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk