This dissertation covers several atomistic modeling techniques and applications in various fields that were classified into two major categories: quantum chemistry and reactive molecular modeling for materials designs (Chapters 2-4) and protein simulation for biological systems (Chapter 5-7). Despite the differences in modeling techniques and application areas with the two categories, all studies employed atomistic simulations to characterize the structures, thermodynamics, and kinetics of the systems of interest, helped understand the fundamental mechanics and driving forces of materials/proteins behaviors that cannot be solely described by experiments, and predicted optimal processing conditions or molecular structures following the process-structure-property relationship.The fundamentals of density functional theory (DFT) and molecular dynamics (MD) simulations are introduced in Chapter 1. DFT is a computational modeling method that is based on quantum mechanics and investigate the electronics structure of many-body systems, which allows for the understanding of atomic bonding and reaction mechanisms. However, its limitations in time scale and length scale made it unsuitable for applications where dynamics is important and reactions happen with larger molecules or systems. Therefore, we utilized reactive MD by parametrizing empirical reactive force fields, Tersoff and ReaxFF, to study the structure changes, reaction mechanisms, and thermodynamic and kinetic properties of surface modification, aqueous reaction, and photo-initiated polymerization. The force fields were fitted against DFT-calculated structures, atomic charges, and energetics, and detailed DFT methods, parametrization algorithms and process, and ReaxFF formalism were described in Chapter 1.
Chapter 2 focuses on applying the above techniques to develop a Tersoff force field for atomic layer etching where incident chlorine adsorbed on germanium (001) surface and modified the surface, followed by energetic Argon bombardment. Reactive MD simulations were then carried out using the developed Tersoff force field to study the correlations between the chlorination energy and penetration depth/ surface coverage, and the Ar bombardment energy and etched product species. Threshold bombardment energy and completion bombardment energy were also determined. This was a collaborative project with Lam Research, and our computational study gave insights with experimental parameters optimization. Chapter 3 focuses on the development of a ReaxFF force field for validating the reaction mechanism of a novel CO2 absorbent – phosphoenol pyruvate (PEP). MD simulations with this force field described the process where PEP in water transferred bicarbonate, which was converted from CO2, into carboxyphosphate and enolate, and investigated the correlation between the phosphorous’ reactivity and partial charge. Chapter 4 focuses on the development of a ReaxFF force field for photo-initiated acrylate free-radical polymerization. This is a collaborative project with the volumetric additive manufacturing (VAM) team in Lawrence Livermore National Lab, as photopolymer resin design is a crucial part in the VAM process. MD simulations with this force field compared the structures and dynamic properties of three acrylates with different numbers of vinyl groups, sizes and shapes, and depicted their polymerization processes. This study not only provided a reactive force field suitable for acrylate polymerization, but also enabled future benchmark studies for resin materials selection.
Chapter 5-7 are the works that studied the interactions between the glycosylated recombinant ACE2 and the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein. In Chapter 5 we developed fully glycosylated computational models of ACE2-Fc fusion proteins that were therapeutically designed to neutralize SARS-CoV-2 spike protein, and this study was further extended to investigate the relationship between glycosylation and the binding of SARS-CoV-2 spike to ACE2 in Chapter 6. Two different glycovariants of ACE2 were built, pulling simulation were conducted for the binding strength between SARS-CoV-2 spike and ACE2, and hydrogen bond interactions analysis and spatial analysis of glycan interactions were used to study the binding regimes under the influence of glycans. These computational analyses offer insights for future designs of glycoproteins as therapeutic baits. The final Chapter 7 focuses on a collaborative work where we performed structural stability comparisons of various spike truncations that are experimentally synthesized in Chinese hamster ovary cells for therapeutic and diagnostic applications.
