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Determination of the structural ensemble of the molten globule state of a protein by computer simulations |
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| Authors: | Masahiro Shimizu Yukihito Kajikawa Kunihiro Kuwajima Christopher M Dobson Yuko Okamoto |
| Institution: | 1. Department of Physics, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan;2. Department of Physics, Graduate School of Science, University of Tokyo, Tokyo, Japan
School of Computational Sciences, Korea Institute for Advanced Study (KIAS), Seoul, Korea;3. Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK |
| Abstract: | We have used computer simulations to investigate the structural nature of the molten globule (MG) state of canine milk lysozyme. To sample the conformational space efficiently, we performed replica-exchange umbrella sampling simulations with the radius of gyration as a reaction coordinate. We applied the Weighted Histogram Analysis Method to the trajectory of the simulations to obtain the potential of mean force, from which we identified representative structures corresponding to local minima in the free energy surface. The representative structures obtained in this way are in accord with the characteristics of the MG state reported previously by experimental studies. We conjecture that the MG state comprises a series of partially structured states undergoing relatively fast conformational interchange. |
| Keywords: | canine milk lysozyme folding intermediate state generalized-ensemble algorithm molecular dynamics simulation molten globule protein folding replica-exchange umbrella sampling |