UC Davis

The exploration of reaction pathways and mechanisms is an important part of computationalchemistry. With known reactant molecules and condition it is always intriguing to predict the product, study the mechanism and calculate different chemical properties to match the experimental results. However, due to the limit of computational resources and theory development, it is hard to simulate all reactions with ideal level of theory and simulation time length to overcome energy barriers for desired product. Meanwhile, different computational softwares also have respective disadvantages, which requires scientific programming and problem-solving skills to fix during the research. In chapter one of this thesis, a simple introduction of computational chemistry is written as prerequisite information about all the work. Chapter two and three are projects aiming at a biochemical system with copper, C-peptide and serum albumin. In this work, we propose the structural model of copper binding site in each compound and calculate the UV-Vis spectra which have a good agreement with published experimental results. A new energy-penalty geometry optimization method is proposed for searching the specific structures of desired absorbance. A hypothetical ternary complex containing all three species is tested with this method and provides good agreement with experiments. Effects that determine UV-Vis absorbance of Cu(II)-protein compound is also suggested. A dummy atom copper model is implemented in OPLS-AA force field for Cu(II) molecular dynamics simulation. By tuning the non-bonded interaction between Cu(II) and residue in protein, structure of binding sites in protein&C-peptide are successfully reproduced. Meanwhile, a good match between binding free energy calculations and experiment is obtained. Part of the results are published in: San Juan, J. A. et al. Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin. J. Am. Chem. Soc. 145, 16726–16738 (2023). Remaining results are scheduled to be submitted very soon. Chapter three is a project focusing on methanol to olefin (MTO) reaction. By using the nanoreactor technique in ab initio molecular dynamics simulations, two experiment detected mechanisms are confirmed with corresponding transition states. QM/MM method is also applied for reaching the balance between accuracy and cost of the simulation. In order to simplify the preparing procedure of running QM/MM calculation on software TeraChem, a simple workflow is proposed for non standard residue to generate necessary input files. Nanoreactor code in TeraChem is also modified to accommodate the QM/MM method.