At the interface of experiment and computation: Explorations of heme protein redox partner interactions, water behavior on organic surfaces and other systems.

摘要

In part one of this thesis, the interactions and resulting complexes between heme proteins and their associated electron-transferring redox partner proteins, termed here as heme protein redox partners, are carefully studied. Such complexes navigate a delicate balance between achieving fast turnover and tight, specific binding. To probe how Nature has balanced these seemingly opposing forces, a series of studies were conducted on three separate heme protein redox partner systems that have achieved a working balance using different approaches; Cytochrome P450cam and its redox partner putidaredoxin, Leishmania major peroxidase and its partner Leishmania major cytochrome c and finally the multi-domain nitric oxide synthase. Each system was initially probed using computational methods including molecular dynamics, Brownian dynamics, and modeling before being experimentally validated against previous findings, novel studies or both.;In part two, the focus is shifted from protein interactions to water behavior on organic surfaces. Studying the behavior of water on such organic surfaces can have wide-ranging impacts on our understanding of not only fundamental water dynamics, but also atmospheric chemistry and chemistry on urban surfaces. Self-assembled monolayers (or SAMs) have long served as a model system to probe how differences in organic surface chemistry may affect water behavior. To this point, the behavior of water on a variety of SAMs were investigated using molecular dynamics in a series of studies including one with experimental validation to deepen our understanding of the dependence of water behavior on the structural makeup of both a pristine idealized surface and more realistic defective SAM systems.;Finally, three additional separate studies are presented in the third and last part of this thesis. These distinct and independent studies 1) cover the conformational dependence of a central protein residue on the conformation of its neighbors, 2) computationally study the binding of a membrane associated protein to a target lipid in a lipid bilayer and 3) experimentally determine the crystal structure of Bacilus subtillis arginase. When combined with the two series of studies previously presented in this thesis, the great potential in applying a combined experimental and computational approach to address unanswered questions is highlighted and explored.