Understanding Protein Cold Denaturation with Molecular Dynamics Simulations


The deformation of proteins under the impact of high temperature has been the main interest of many biochemical researches. However, very little is known about protein’s behavior at low temperature. In recent years, when the computation power is dramatically improved to allow the simulations of seemingly impossible experimental conditions, cold denaturation starts raising questions in the curious mind of scientists. My summer research aimed at modifying a coarse-grained implicit-solvent protein model so that it could correctly capture all the side chain-side chain and side chain-backbone interactions, using the basic theories of Molecular Dynamics (MD) simulations. The model that I was working on originated from the previously proven models, namely Warshel and Mercedes-Benz. I experimented with building in a new parameter that took into account the temperature-dependent hydration enthalpy of the system. While the project currently requires some revision, the ultimate goal is to create a model which denatures at low temperature. I envision the next step to be the incorporation of the crowding agents, which mimic the cellular environment, allowing more precise understanding of proteins’ behavior in vivo.