title: Beta-hairpins with native-like and non-native hydrogen bonding patterns could form during the refolding of staphylococcal nuclease.
abstract: Refolding of staphylococcal nuclease has been studied recently by hydrogen-deuterium exchange and NMR spectroscopy. These studies infer that beta-hairpin formed by strand 2 and strand 3 connected by reverse turn forms early during the refolding of nuclease. Typically, hydrogen-deuterium exchange NMR techniques are usually carried out on a time scale of milliseconds whereas beta-hairpins are known to fold on a much shorter time scale. It follows that in the experiments, the hydrogen-deuterium exchange protection patterns could be arising from a significant population of fully formed hairpins. In order to demonstrate it is the fully formed hairpins which gives rise to the hydrogen-deuterium exchange protection patterns, we have considered molecular dynamics simulation of the peptide (21)DTVKLMYKGQPMTFR(35) from staphylococcal nuclease corresponding to the beta-hairpin region, using GROMOS96 force field under NVT conditions. Starting from unfolded conformational states, the peptide folds into hairpin conformations with native-like and non-native hydrogen bonding patterns. Subsequent to folding, equilibrium conditions prevail. The computed protection factors and atom depth values, at equilibrium, of the various amide protons agree qualitatively with experimental observations. A collection of molecules following the trajectories observed in the simulations can account for experimental observations. These simulations provide a molecular picture of the formed hairpins and their conformational features during the refolding experiments on nuclease, monitored by hydrogen-deuterium exchange.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Patel
authors.forename: Prakash
authors.initials: P
authors.lastname: Sista
authors.forename: Petety V
authors.initials: PV
authors.lastname: Balaji
authors.forename: Yellamraju U
authors.initials: YU
authors.lastname: Sasidhar
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D041961:Deuterium Exchange Measurement; D006860:Hydrogen Bonding; D008836:Micrococcal Nuclease / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; D008836:Micrococcal Nuclease