Beta-hairpins with native-like and non-native hydrogen bonding patterns could form during the refolding of staphylococcal nuclease |
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Authors: | Patel Sunita Sista Prakash Balaji Petety V Sasidhar Yellamraju U |
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Affiliation: | Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. |
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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. |
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