Pressure-Dependent Collapsibility of Proteins: The Impact of Topology and Length

Many efforts have been made to find the physics that guides amino acid sequences to fold to their native structure. It has been shown that the “foldability” of a sequence is directly related to its “collapsibility”. Thus, studying the “collapsibility” of a sequence is essential to understand its folding. The theory of collapsibility [1] demonstrates that the propensity of a sequence to collapse is linked to the native state topology, implying that natural selection favors those sequences that are compact. In this study, we use pressure perturbation to interrogate this relation. We extended the model by taking into account the solvent-induced desolvation barrier and its pressure dependence. We show that while pressure denatures fully folded states, proteins still tend to collapse to a water-mediated state, with topology playing a dominant role in the pressure dependence of the process. Generally speaking, proteins with more non-local contact interactions are more sensitive to pressure. The average change in water-mediated enhances collapsibility in proteins with more longer-range interactions is significantly greater. This shows that as pressure increases, proteins with relatively longer-range interactions are more prone to changing to a water-mediated collapsed state. Our study generalizes the notion of collapsibility, and relates it to the dependence on topology, thus providing further insights into the pressure dependence of collapsibility.



[1] Samanta et al, Soft Matter 13, 3622 (2017).