Classical Force Field Simulations of Biological Processes and Quantum Chemical Computations of Homogeneous Catalysts

Abstract

Computational chemistry methods and tools have enabled studies of biological processes and chemical reactions to get insights from detailed atomic structures and reaction mechanisms. In this thesis, two biological problems are attacked by the classical force fields simulations and two homogeneous catalysis problems are studied by quantum chemical calculations. In all four problems, new insights have been revealed by the computational results. Chapter 1 briefly reviews the computational chemistry theories and methods developed and popularized in the past few decades. Chapter 2 addresses the protein-protein interaction problem in the onset of meningitis where E. coli OmpA interacts with FcγRI α-chain (FcγRIa) to invade macrophages. Computationally predicted three-dimensional structure of the OmpA-FcγRIa complex showed the role of three N-glycans in FcγRIa in the interaction. Chapter 3 studies the molecular origin of the bitter aftertaste of a kind of natural sweetener called steviol glycosides. By examining the predicted binding complexes between the human bitter taste receptors 2R4 and 2R14 which could be activated by steviol glycosides, a general activation model is proposed to explain the structure-function relationship and to predict new natural sweeteners with less bitterness. Chapter 4 investigated the reaction mechanisms of methane to methanol conversion by a biomimetic tricopper cluster compound. An unusual exchange-stabilized multiradical state is found to be responsible for the hydrogen abstraction reactivity and a methyl radical rebound mechanism is proposed for methane oxidation. Calculations also show interesting spin crossing during the reaction cycle with high spin state forbidden for methyl rebound. Chapter 5 examines the reaction mechanisms in olefin hydrosilylation by the Pt-based Karstedt’s catalyst. An unexpected rate-determining step of agostic bond dissociation is found in between the elementary reaction steps proposed previously. The regioselectivity of the products are studied. An alternative reaction cycle which is kinetically unflavored is proposed. Oxygen stability is studied.