Behavior of Proteins under Pressure from Experimental Pressure-Dependent Structures

Abstract

Structure-based models are coarse-grained representations of the interactions responsible for the protein folding process. In their simplest form, they use only the native contact map of a given protein to predict the main features of its folding process by computer simulation. Given their limitations, these models are frequently complemented with sequence-dependent contributions or additional information. Specifically, to analyze the effect of pressure on the folding/unfolding transition, special forms of these interaction potentials are employed, which may a priori determine the outcome of the simulations. In this work, we have tried to keep the original simplicity of structure-based models. Therefore, we have used folded structures that have been experimentally determined at different pressures to define native contact maps and thus interactions dependent on pressure. Despite the apparently tiny structural differences induced by pressure, our simulation results provide different thermodynamic and kinetic behaviors, which roughly correspond to experimental observations (when there is a possible comparison) of two proteins used as benchmarks, hen egg-white lysozyme and dihydrofolate reductase. Therefore, this work shows the feasibility of using experimental native structures at different pressures to analyze the global effects of this physical property on the protein folding process.

Effects of sequence-dependent non-native interactions in equilibrium and kinetic folding properties of knotted proteins

“…This is not just a technical detail of the model since very narrow transitions, which lead to artificially large cooperativity, are poorly sampled in equilibrium simulations that use a replica exchange procedure as done here [16,26,27]. The width proposed above has been successfully used in previous simulations employing a similar potential and sampling [16,17,28,29]. When this potential is used, we consider that a native contact is formed if the distance between the centers of the respective beads differs from the distance between their C-alpha atoms in the native conformation by less than the half-width of the potential wells, w.…”

“…In the case of protein MJ0366 the equivalent interactions involve residues located on the stretches (17)(18) and (53-56). The interactions that stabilize the knot in the case of Rds3p appear to be more plastic than in the other two proteins although there is some level of conservation for the regions (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) and (63-76). Figure 6 highlights these regions in the three-dimensional native structures of the three proteins.…”