Phase Phenomena of Proteins in Living Matter
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Proteins must fold and function in the immensely complex environment of a cell, i.e. the cytoplasm—this is far from the ideal test-tube setting of a dilute solution. Here, this thesis answers an important question at the interface of physics and biology: how does the crowded cellular environment influence the dynamics of individual proteins and their folding phases? This thesis is presented in two parts. First, we review protein folding and investigate the effects of hydrostatic pressure using coarse-grained molecular simulations. There are two common forms of pressure-dependent potentials of mean force (PMFs) derived from hydrophobic molecules available for coarse-grained molecular simulations of protein folding and unfolding under hydrostatic pressure. We investigated the two different pressure-dependencies on the desolvation potential in a structure-based protein model using coarse-grained molecular simulations. We compared the simulation results to the known behavior of proteins based on experimental evidence. We showed that the protein’s folding transition curve on the pressure–temperature phase diagram depends on the relationship between the potential well minima and pressure. For a protein that reduces its total volume under pressure, the PMF needs to carry the feature that the direct contact well is less stable than the water-mediated contact well at high pressure. In the second part we move toward understanding the effects of crowded environment of the cell. Proteins have properties that are exhibited by systems near a critical point, where distinct phases merge. This concept goes beyond previous studies that propose proteins have a well-defined folded and unfolded phase boundary in the pressure-temperature plane. Here, by modeling the protein phosphoglycerate kinase (PGK) on the temperature (