Author ORCID Identifier


Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Samer Gozem


Flavin is the cofactor for the large and diverse family of proteins called flavoproteins. Upon absorption of blue light, the flavin cofactor may undergo one of several potential photophysical processes, depending on the surrounding environment. Possible photophysical processes include fluorescence from the first singlet excited state (S1), intersystem crossing to a long-lived triplet state (T1), or photoreduction to form a radical species (D1). Each of those processes has been exploited for applications such as biosensing, bioimaging, FRET process, optogenetics, and singlet oxygen generation. However, the dependence of flavin’s photophysics (mechanism and kinetics) on its protein environment is not well understood. As a step towards developing this understanding, we simulated UV-vis and FT-IR spectra of flavin in a different polar environment to understand the effect of hydrogen bonding interaction on absorption and fluorescence energies and the vibrational frequencies of flavin. We also generated electrostatic spectral tuning maps (ESTMs) for each of flavin’s redox and protonation states to see how electrostatics influence their energetics. We also developed an automated quantum mechanical/molecular mechanical (QM/MM) protocol for simulating flavoproteins. With the guide of ESTMs and the QM/MM calculations, we focus on studying the spectral tuning of iLOV, an engineered flavin-binding fluorescent protein. Specifically, we suggest a novel mutant iLOV-Q430E that provides a red-shifted absorption and fluorescence maximum wavelength, which has been experimentally verified.


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