This thesis aims to provide an understanding of computational methods for modeling light-matter interactions through the lens of UV-visible spectroscopy and excitation energy transfer processes. Chapter 1 lays down the foundation of fundamentals required to understand the basics of electronic structure theory and UV-visible spectroscopy. Chapter 2 provides an overview of DFT and various functional approximations, followed by my density functional benchmark study for vibronic spectra in both implicit and explicit solvent environments. Chapter 3 introduces the combined ensemble Franck-Condon (E-FC) method, a practical tool for modeling UV-visible spectra of molecules in explicit solvent environments, where I have extended and generalized the E-FC methods for the first time to compute the fluorescence spectra of molecules in an explicit solvent environment. This hybrid method, developed by merging the advantages of nuclear ensemble and Franck-Condon methods, effectively incorporates the influence of molecular configurations in an explicit solvent environment with vibronic coupling. Chapter 4 showcases the application of E-FC methods to calculate the UV-visible spectra of three commonly used dyes: NBD and NR in DMSO and 7MC in Methanol. Additionally, we compare the performance of the family of E-FC methods, namely E-sumFTFC, Eopt-avgFTFC, and E-avgZTFC, with each other. The chapter concludes with results indicating a significant improvement over traditional linear optical spectroscopy methods. We also compare the computed absorption and fluorescence lineshapes with experimental data, validating the accuracy of our results and discussing the relative computational efficiency of these methods.
Chapter 5 compares Coulombic coupling values computed using various methods for NBD-NR and CV$+$ dimer systems involved in the excitation energy transfer process both in an implicit and explicit solvent environment. The methods used include coupling via transition dipole moments, transition charges, and transition densities from both isolated dyes and supramolecular systems. We compare the relative accuracy of these methods for both systems. The results presented in this section represent ongoing progress on the project and will be included in a future paper.
Chapter 6 summarizes the project carried out during the summer of 2023 as an intern in the computational chemistry division at Frontier Medicines, San Francisco. The project aimed to develop a computational procedure to rank-order potent ligands bound to Bruton's Tyrosine Kinase (BTK) using their relative binding free energies (RBFEs). The chapter introduces BTK and its role in signaling pathways, the computational procedure used, the results, and a discussion on the impact of the protein region definition on RBFE. It concludes with recommendations for improved RBFE calculations.
