Toward an Understanding of the Retinal Chromophore in Rhodopsin Mimics

Abstract

Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combined computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (λ(a)max), fluorescence (λ(f)max), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore.

Tuning the Protein‐Induced Absorption Shifts of Retinal in Engineered Rhodopsin Mimics

“…They further emphasized that isolation of the retinal from water is essential for electrostatic tuning of the retinal. In a study of an earlier generation of rhodopsin mimics, Huntress et al . found that limited molecular dynamics sampling is an issue when loosely bound water molecules are near the retinal.…”

Analytical First and Second Derivatives for a Fully Polarizable QM/Classical Hamiltonian

“…76 Figure 3 reports a pictorial view of optimized geometries as calculated by exploiting a hierarchy of models to account for the environment. The QM portion (the retinal) was treated at the B3LYP/6-31G* level, and the MM portion was held fixed.…”

Advances in understanding the molecular basis of the first steps in color vision

“…Systematic mutagenesis of amino acids close to the chromophore led to absorption spectra ranging from 425 nm up to 644 nm (Sakmar, 2012; Wang et al, 2012). The described artificial spectral tuning through the cellular retinol-binding protein II gave insights into the correlation between electrostatic effects, counter anion, structure of 11- cis -retinal and absorbed wavelength (Huntress et al, 2013). An artificially engineered system such as this experiment demonstrates is the marked ability of 11- cis -retinal to absorb light over a broad spectrum.…”