Date of Award
Doctor of Philosophy (PhD)
Physics and Astronomy
In this dissertation, we study the role of electrostatics in molecular recognition, ion binding and pH-dependent phenomena. In this work that includes three different research projects, the Poisson-Boltzmann (PB) model is used to describe the biological system and Delphi (which is a popular tool for solving the PB equation (PBE)) to study the electrostatics of biomolecular systems.
Chapter two aims to investigate the role of electrostatic forces in molecular recognition. We calculated electrostatic forces between binding partners separated at various distances. To accomplish this goal, we developed a method to find an appropriate direction to move one chain of protein complexes away from its bound position, and then calculated the corresponding electrostatic force as a function of separation distance. Based on the electrostatic force profile (force as a function of distance), we grouped the cases into four distinct categories.
Chapter three reports a new release of a computational method, the BION-2 method, that predicts the positions of non-specifically surface-bound ions. The BION-2 utilizes the Gaussian-based treatment of ions within the framework of the modified Poisson–Boltzmann equation, which does not require a sharp boundary between the protein and water phase. Thus, the predictions are done by the balance of the energy of interaction between the protein charges and the corresponding ions and the de-solvation penalty of the ions as they approach the protein. The BION-2 is tested against experimentally determined ions’ positions, demonstrating that it outperforms the old BION and other available tools.
Chapter four focuses on computationally investigating the pH-dependent stability of several melanosomal membrane proteins and comparing them to the pH dependence of the stability of TYR. We confirmed that the pH optimum of TYR is neutral, and we also found that proteins that are negative regulators of melanosomal pH are predicted to function optimally at neutral pH. In contrast, positive pH regulators were predicted to have an acidic pH optimum.
Hewa Bosthanthirige, Mihiri, "Revealing the Role of Electrostatics in Molecular Recognition, Ion Binding and pH-Dependent Phenomena" (2022). All Dissertations. 3094.
Author ORCID Identifier