Molecular dynamics study of unfolding of lysozyme in water and its mixtures with dimethyl sulfoxide

All-atom explicit solvent molecular dynamics was used to study the process of unfolding of hen egg white lysozyme in water and mixtures of water with dimethyl sulfoxide at different compositions. We have determined the kinetic parameters of unfolding at a constant temperature 450 K. For each run, the time of disruption of the tertiary structure of lysozyme tu was defined as the moment when a certain structural criterion computed from the trajectory reaches its critical value. A good agreement is observed between the results obtained using several different criteria. The secondary structure according to DSSP calculations is found to be partially unfolded to the moment of disruption of tertiary structure, but some of its elements keep for a long time after that. The values of to averaged over ten 30 ns-long trajectories for each solvent composition are shown to decrease very rapidly with addition of dimethyl sulfoxide, and rather small amounts of dimethyl sulfoxide are found to change the pathway of unfolding. In pure water, despite the loss of tertiary contacts and disruption of secondary structure elements, the protein preserves its compact globular state at least over 130 ns of simulation, while even at 5 mol percents of dimethyl sulfoxide it loses its compactness within 30 ns. The proposed methodology is a generally applicable tool to quantify the rate of protein unfolding in simulation studies. (C) 2017 Elsevier Inc. All rights reserved.