The Role Of Water On Conformational Dynamics Of Barstar Protein

Protein dynamics is critical for their functions and evolvability, and is to a greatextent determined by the roughness of their potential energy surface (PES). Solventsplay an indispensable role in shaping dynamic behaviour of proteins throughmolecular interactions that modify protein PES. Two lines of evidences have beenpresented by many experimental and computational reports supporting eithermediating or slaving roles of water molecules.Therefore, reconciling mediating andslaving roles of water in protein conformational dynamics is of great theoretical andpractical importance. In this study, by systematically analysing the time series (orevolution in conformational space) of relevant energy terms (protein self energy (Ep),protein-water interactions (Ep-w) and their sums (Etot)) obtained from MDtrajectories, we found that while the negative correlation between Ep and Ep-w inmost parts of conformational space provides possibility for PES smoothing, thedominance of sigma(Ep-w) over sigma(Ep)(sigma stands for standard deviation)resulting in a rougher PES on average, especially for picoseconds and longer timescales. These two aspects contribute to the end effects of water molecules on the PESof proteins，that is roughening the majority and smoothing the remainingpart of thepotential energy landscape. Thus, the conicting roles of water in theproteinconformational dynamics are reconciled with an energy landscape perspective.It isnoted here that due to the constraint of computational resource, our analysis werelimited to sub-microsecond time scale, correspond to transitions covering a fewhierarchies of statistical substates. The impact of water molecules on major domainmotions that occur on milli-seconds and longer time scales and folding dynamics isbeyond the scope of this study.