Doctor of Philosophy (Ph.D.), Bowling Green State University, 2019, Photochemical Sciences

The primary event in vision is induced by the ultrafast photoisomerization of rhodopsin, the dim-light visual pigment of vertebrates. While spectroscopic and theoretical studies have identified certain vibrationally coherent atomic motions to promote the rhodopsin photoisomerization, how exactly and to what degree such coherence is biologically related with its isomerizing efficiency (i.e. the photoisomerization quantum yield) remains unknown. In fact, in the past, the computational cost limited the simulation of the rhodopsin photoisomerization dynamics, which could be carried out only for a single molecule or a small set of molecules, therefore lacking the necessary statistical description of a molecular population motion. In this Dissertation I apply a hybrid quantum mechanics/molecular mechanics (QM/MM) models of bovine rhodopsin, the verterbrate visual pigment, to tackle the basic issues mentioned above. Accordingly, my work has been developing along three different lines comprising the development, testing and application of new tools for population dynamics simulation: (I) Development of a suitable protocol to investigate the excited state population dynamics of rhodopsins at room temperature. (II) A correlation between the phase of a hydrogen-out-of-plane (HOOP) motion at the decay point and the outcome of the rhodopsin photoisomerization. (III) A population “splitting” mechanism adopted by the protein to maximize its quantum yield and, therefore, light sensitivity. In conclusion, my Dissertation reports, for the first time, a connection between the initial coherent motion of a population of rhodopsin molecules and the quantum efficiency of their isomerization. The photoisomerization efficiency is ultimately determined by the way in which the degree of coherence of the excited state population motion is modulated by the protein sequence and conformation.

Committee: Massimo Olivucci Ph.D (Advisor); Andrew Gregory Ph.D (Other); Hong Lu Ph.D (Committee Member); Alexey Zayak Ph.D (Committee Member) Subjects: Biochemistry; Chemistry

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2018, Photochemical Sciences

The need for a detailed mechanistic understanding of the photoisomerization of retinal chromophore (retinal protonated Schiff base, rPSB) is becoming increasingly important, not only due to its fundamental importance in vision but also owing to the growing number of applications in various fields. The development of microbial rhodopsin based fluorescent probes and actuators essential in neuroscience, synthetic bio-mimetic molecular switches and motors useful in material science and synthetic biology are examples of such applications. The work presented in this dissertation is devoted to unveil and understand a novel mechanistic factor with significant impact on the photoisomerization of rPSB-like systems. This factor corresponds to the interaction between the first electronic excited state and higher states (usually the second excited state) occurring during the excited state lifetime or, in other words, along the excited state photoisomerization coordinate. This "electronic state mixing" effect is studied by employing different computer tools including hybrid quantum mechanics/molecular mechanics (QM/MM) methods. The investigated systems include representative animal and microbial rhodopsins, bio-mimetic N-alkyl-indanylidene-pyrrolinium (NAIP) molecular switches and a recently reported water soluble rhodopsin mimic. Our results unveil two type of effects due to changes in the electronic mixing: an impact on the excited state lifetime and an impact on vibrational coherence as we now briefly describe. The impact on excited state lifetime is first demonstrated by uncovering the variation of rPSB photoisomerization speed in different environments is due to an increase or decrease of electronic state mixing and that this effect can be controlled by the electrostatic field of the environment. This leads us to hypothesize that animal rhodopsins, which isomerize within 200 fs, have been evolved to minimize the electronic state mixing such that biological functions are car (open full item for complete abstract)

Committee: Massimo Olivucci Ph.D (Advisor); Alexander Tarnovsky Ph.D (Committee Member); R. Marshall Wilson Ph.D (Committee Member); Salim Elwazani Ph.D (Other) Subjects: Biophysics; Chemistry; Organic Chemistry; Physical Chemistry