Anisotropic Protein Interactions in Salt Solutions and at Interfaces: Coarse Grained Modeling
Sammanfattning: Anisotropic protein interactions have a strong orientation dependence resulting from an uneven distribution of charged and hydrophobic residues on the protein surface. They play an important role in protein behaviors such as protein association, surface adsorption and phase separation. In this thesis, we have studied the effect of anisotropic interactions on the behavior of various proteins mainly by focusing on electrostatic interactions. We have developed coarse grained models, specific to each system by considering their essential details and used Metropolis Monte Carlo method to simulate protein behaviors in salt solutions and at charged interfaces. We show that anisotropic dipolar interactions may overcome the net charge repulsion between similarly charged proteins and favor the protein association. The strong directionality of these interactions may reinforce specific protein orientations, required for protein activity. Note that hydrophobic anisotropy can also compete with the directionality of the dipolar interactions and may force the proteins into less favorable dipole orientations. We also show that the charge regulation effects and the specific Hofmeister ion binding can significantly alter the charge distribution of proteins, and thus they should not be overlooked in the studies of protein electrostatics. Our results indicate that to gain a comprehensive understanding of protein electrostatics, one needs to consider: (i) the higher order multipole interactions; (ii) the hydrophobic patchiness that can compete with the multipole interactions; (iii) the charge regulation effects; as well as (iv) the specific ion binding. The extent of these factors can roughly be estimated by examining the dipole moment, the locations of hydrophobic patches, the number of residues with acid dissociation constants around solution pH as well as the concentration of binding ions and the exposed area of their binding sites.
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