The color of rhodopsins at theab initiomulticonfigurational perturbation theory resolution

Abstract

We demonstrate that ''brute force'' quantum-mechanics͞molecu-lar-mechanics computations based on ab initio (i.e., first principles) multiconfigurational perturbation theory can reproduce the absorption maxima of a set of modified bovine rhodopsins with an accuracy allowing for the analysis of the factors determining their colors. In particular, we show that the theory accounts for the changes in excitation energy even when the proteins display the same charge distribution. Three color-tuning mechanisms, leading to changes of close magnitude, are demonstrated to operate in these conditions. The first is based on the change of the conformation of the conjugated backbone of the retinal chromophore. The second operates through the control of the distance between the positive charge residing on the chromophore and the carboxylate counterion. Finally, the third mechanism operates through the changes in orientation of the chromophore relative to the protein. These results offer perspectives for the unbiased computational design of mutants or chemically modified proteins with wanted optical properties.excited states ͉ quantum mechanics͞molecular mechanics R ecently, protein mutants displaying properties such as high binding affinities and novel catalytic activities (1, 2) have been designed by using computational methods based on molecular mechanics. In a close context, substrate selectivity has been simulated by using more advanced tools based on density functional theory and molecular mechanics paving the way to the design of mutations that convert receptors into enzymes (3). However, the design of mutants with specific spectral properties, such as color and luminescence, represents a more complex problem. In these cases, the quantum chemical method used must be capable to describe both ground and electronically excited states of the protein chromophore. The ab initio (i.e., first-principles) complete-active-space self-consistent-field (CASSCF) method (4) is a multiconfigurational method offering maximum flexibility for an unbiased description of the electronic and equilibrium structure of a molecule (i.e., with no empirically derived parameters and avoiding single-reference wavefunctions). Furthermore, the CASSCF wave function can be used for subsequent multiconfigurational second-order perturbation theory (5) computations (CASPT2) of the dynamic correlation energy of each state ultimately leading to a nearly quantitative evaluation of the excitation energies of organic compounds (6, 7). The CASPT2 ability to describe exotic bonding has been recently assessed (8).In a previous study (9), we implemented the ab initio CASPT2͞͞CASSCF protocol (where equilibrium geometries and electronic energies are determined at the CASSCF and CASPT2 levels, respectively) in a quantum mechanics͞ molecular mechanics (QM͞MM) scheme (10-12) allowing for the evaluation of the excitation energy of chromophores (treated quantum mechanically) embedded in a protein environment (described by a MM force field).The absorption and fluorescence max...

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

“…Globally, the 27 residues in the cavity generate a blue shift of 10 kcal mol −1 , which results from large blue-shifting E113 effect contrasted by a cluster of residues creating a positive potential on the Schiff base region. This is consistent with the idea of a substantially "localized" counterion structure in Rh whose effect is partially quenched by the remaining opsin residues as also reported in previous studies using similar models (29,40,42).…”

“…As also observed in hMeOp and sqRh, nonpolar amino acids are mainly located around the β-ionone ring. In line with previous results (40)(41)(42)), the Rh model shows that the largest electrostatic effect is due to the putative E113 counterion (SI Appendix, Fig. S6).…”

“…S220 has instead an opposite effect. The computed ΔE S1-S0 changes are explained by considering that upon vertical excitation, ∼30% of the positive charge localized in the C=N region of the backbone is translocated toward the β-ionone ring (40). Therefore, residues creating a negative (positive) electrostatic potential in the Schiff base region would stabilize (destabilize) the S 0 state with respect to S 1 .…”

Assessment of semiempirical methods for the photoisomerisation of a protonated Schiff base

“…CASPT2//CASSCF has further been used to calculate the excitation energies [12] and absorption spectra [13,14] of retinal in the full protein environment using a combined quantum mechanical/ molecular mechanical (QM/MM) description. The conical intersection of rhodopsin has also been characterised using this technique [15].…”

Polarizable Embedding Density Matrix Renormalization Group

“…This system has become a benchmark system for advanced electronic structure methods in recent years (see, for instance, Refs. [103][104][105][106][107][108][109][110][111][112][113][114][115][116][117]. For the channelrhodopsin protein, we employ the M2P2 potential constructed in Ref.…”