Date of Award
6-26-2026
Date Published
July 2026
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Advisor(s)
Atanu Acharya
Subject Categories
Chemistry | Physical Sciences and Mathematics
Abstract
A redox process involves electron transfer between a donor and an acceptor, resulting in changes in oxidation states. In biological systems, redox properties are strongly influenced by the surrounding protein environment. Environmental fluctuations induce variations in electrostatics interactions, polarization, and hydrogen-bond networks that directly modulate the energy gap between electronic states. Computational approaches are necessary to decompose environmental contributions at atomic resolution and for systems that are difficult to characterize experimentally. This requires extensive conformational sampling and a reliable treatment of electronic structure and environmental polarization. Small errors in them can lead to significant deviations in computed redox properties. To address these challenges, this thesis investigates how conformational sampling strategies affect the computed redox properties. The redox properties of the one-electron oxidation processes are calculated for small, biologically relevant redox-active molecules (e.g., phenol, phenolate, benzene, indole, lumiflavin) in aqueous solution using both molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations. In QM/MM energy-gap sampling, the effect of the QM region size on overall redox behavior was also evaluated. The observed free energy of oxidation, and consequently, oxidation potential differs consistently by ~0.2-0.4 V between QM/MM and MM sampling for the molecules under investigation. This results infer that computationally cheaper MM sampling would be adequate for computing the redox properties of small molecules when corrected by a system-specific correction factor. Beyond local redox properties, this thesis investigates long-range photoinduced allosteric communication between a blue light using flavin (BLUF) domain and a distant adenylyl cyclase (AC) domain in the photoactivated adenylyl cyclases (PAC) from Beggiatoa sp. (bPAC). Although photoactivation of the BLUF domain induces only minimal structural changes, it activates a chemical reaction about 4-5 nm away. Here, we combine molecular dynamics simulations, electronic structure calculations, network analysis, and machine-learning approaches to investigate photoinduced allostery in bPAC. We observed that the photoexcitation enables electron transfer from a conserved tyrosine (Tyr7) to the flavin isoalloxazine ring, while the free energy of the electron transfer remains similar across active and inactive mutants. Therefore, photoinduced allosteric activity arises from conformational effects rather than changes in the electronic parameters. Using network theory and eigenvector centrality analysis, we identified residues relevant to allosteric pathways linking the BLUF and AC domains. Furthermore, we used machine learning (ML) models to distinguish active and inactive conformational states without prior knowledge of functional residues. Remarkably, the ML models identified key regions known from network analysis. Together, these results provide a generalizable framework for understanding allosteric pathways in blue-light-sensitive proteins.
Access
Open Access
Recommended Citation
Maity, Suman, "Redox and Allosteric Processes in Blue Light Sensitive Proteins" (2026). Dissertations - ALL. 2324.
https://surface.syr.edu/etd/2324
