QM/MM study of energy storage and molecular rearrangements due to the primary event in vision - PubMed (original) (raw)

Comparative Study

QM/MM study of energy storage and molecular rearrangements due to the primary event in vision

Jose A Gascon et al. Biophys J. 2004 Nov.

Abstract

The energy storage and the molecular rearrangements due to the primary photochemical event in rhodopsin are investigated by using quantum mechanics/molecular mechanics hybrid methods in conjunction with high-resolution structural data of bovine visual rhodopsin. The analysis of the reactant and product molecular structures reveals the energy storage mechanism as determined by the detailed molecular rearrangements of the retinyl chromophore, including rotation of the (C11-C12) dihedral angle from -11 degrees in the 11-cis isomer to -161 degrees in the all-trans product, where the preferential sense of rotation is determined by the steric interactions between Ala-117 and the polyene chain at the C13 position, torsion of the polyene chain due to steric constraints in the binding pocket, and stretching of the salt bridge between the protonated Schiff base and the Glu-113 counterion by reorientation of the polarized bonds that localize the net positive charge at the Schiff-base linkage. The energy storage, computed at the ONIOM electronic-embedding approach (B3LYP/6-31G*:AMBER) level of theory and the S0-->S1 electronic-excitation energies for the dark and product states, obtained at the ONIOM electronic-embedding approach (TD-B3LYP/6-31G*//B3LYP/6-31G*:AMBER) level of theory, are in very good agreement with experimental data. These results are particularly relevant to the development of a first-principles understanding of the structure-function relations in prototypical G-protein-coupled receptors.

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Figures

FIGURE 1

FIGURE 1

Photoisomerization of the retinyl chromophore in rhodopsin.

FIGURE 2

FIGURE 2

Deviations of the C-α atom coordinates in the rhodopsin molecular structure optimized at the ONIOM-EE (B3LYP/6-31G*:AMBER) level of theory from the corresponding C-α atom coordinates in the x-ray crystal structure. The dotted line indicates the RMS ∼0.83 Å.

FIGURE 3

FIGURE 3

Definition of positive and negative φ(C11–C12) dihedral angles. The retinyl chromophore and the protein chain beyond the Schiff linkage are represented by brown and gray tubes, respectively. The Schiff linkage is highlighted in blue and the C11–C12 bond in magenta. The rotational axis defined by the C11–C12 bond is represented by dashes. Note that the steric interaction of the C13-methyl substituent group with the Ala-117 amino acid hinders the rotation toward positive angles.

FIGURE 4

FIGURE 4

Molecular structures of 11-cis rhodopsin (top panel), with φ(C11–C12) = −11° and all-trans bathorhodopsin (bottom panel), with φ(C11–C12) = −161°.

FIGURE 5

FIGURE 5

Superposition of molecular structures of 11-cis rhodopsin (brown) and all-trans bathorhodopsin (white), optimized at the ONIOM-EE (B3LYP/6-31G*:AMBER) level of theory. The protein chain beyond the Schiff linkage is represented by gray tubes, the Schiff linkage is highlighted in blue and the C11–C12 bond in magenta.

FIGURE 6

FIGURE 6

Superposition of rhodopsin (brown) and bathorhodopsin (white) molecular structure at the Schiff linkage, including the explicit visualization of the distribution of surrounding residues responsible for the most significant electrostatic contributions to the total energy storage (see Fig. 7). The protein chain beyond the Schiff linkage is represented by gray tubes and the Schiff linkage is highlighted in blue. The red-dashed arrows indicate the reorientation of polarized bonds in the retinyl chromophore, responsible for the displacement of the net positive charge at the linkage relative to the Glu-113 counterion, including the N–H+ and C15–H bonds (only the hydrogen atoms of these two bonds are represented by white spheres). The negative charge density is highlighted in blue.

FIGURE 7

FIGURE 7

Electrostatic contribution of each residue to the total energy storage.

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