Title

An Analysis of Artificial Rhodopsin Mimics Using Multiconfigurational Ab Initio Computations

Date of Award

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Photochemical Sciences

First Advisor

Massimo Olivucci

Second Advisor

Alexander Tarnovsky, PhD (Committee Member)

Third Advisor

Neocles Leontis, PhD (Committee Member)

Fourth Advisor

Jong Kwan Lee, PhD (Committee Member)

Abstract

Rhodopsin proteins are found in a wide range of organisms and perform a variety of functions. Vertebrate rhodopsins signal the G-protein transducin in the first step of the visual process while microbial rhodopsins can act as ion pumps or trigger phototaxis. In all varieties it is the retinyl chromophore that endows function to the protein by undergoing a light-initiated isomerization. Using bottom-up engineering, the retinyl chromophore has previously been incorporated into protein frameworks based on Cellular Retinoic Acid Binding Protein II (CRABPII). Two of these “rhodopsin mimics” are studied in this work.

A quantum mechanics / molecular mechanics protocol based on ab initio multiconfigurational quantum chemistry was constructed to model the spectral and dynamic features of rhodopsin mimics. The accuracy of the models is established by showing that computations reproduce the observed absorption maxima of both mutants. The mechanism of spectral tuning is investigated in mutants incorporating a variety of forms of retinyl chromophore, including both the protonated and deprotonated all-trans Schiff base chromophore and non-covalently bound retinal. Exploration of the excited state potential energy surface reveal two minima from which fluorescence can occur in the R132K:R111L:L121E (KLE) mutant of CRABPII, findings which were supported by ultrafast transient absorption spectra that resolved two different evolving S1 populations. The KLE mutant is compared to solvated protonated all-trans retinal Schiff base (PSBAT) and both systems are found to be highly similar in terms of calculated absorption maxima and possible photoreactivity, as ascertained from relaxed scans performed on the KLE mutant.