Molecular Dynamics Study of the Nature and Origin of Retinal's Twisted Structure in Bacteriorhodopsin

Abstract

The planarity of the polyene chain of the retinal chromophore in bacteriorhodopsin is studied using molecular dynamics simulation techniques and applying different force-field parameters and starting crystal structures. The largest deviations from a planar structure are observed for the C(13)==C(14) and C(15)==N(16) double bonds in the retinal Schiff base structure. The other dihedral angles along the polyene chain of the chromophore, although having lower torsional barriers in some cases, do not significantly deviate from the planar structure. The results of the simulations of different mutants of the pigment show that, among the studied amino acids of the binding pocket, the side chain of Trp-86 has the largest impact on the planarity of retinal, and the mutation of this amino acid to alanine leads to chromophore planarity. Deletion of the methyl C(20), removal of a water molecule hydrogen-bonded to H(15), or mutation of other amino acids to alanine did not show any significant influence on the distortion of the chromophore. The results from the present study suggest the importance of the bulky residue of Trp-86 in the isomerization process, in both ground and excited states of the chromophore, and in fine-tuning of the pK(a) of the retinal protonated Schiff base in bacteriorhodopsin. The dark adaptation of the pigment and the last step of the bacteriorhodopsin photocycle imply low barriers against the rotation of the double bonds in the Schiff base region. The twisted double bonds found in the present study are consistent with the proposed mechanism of these ground state isomerization events.

X-ray Crystallographic Structure of Thermophilic Rhodopsin

“…The previously determined force field of the retinal protonated Schiff base was employed for the chromophore (32,33). Long-range electrostatic interactions were treated using the particle mesh Ewald method.…”

Mechanism of a proton pump analyzed with computer simulations

“…2c, d), by the interaction with the negatively charged counterion [54,67,68] (black and blue/cyan curves in Fig. 2), and by pronounced twists around double bonds [38]. The bond alternation is reduced by protonation of the Schiff base [46] (Fig.…”

“…3b). Although retinal is a flexible molecule and it samples a relatively wide range of conformations during dynamics [6,38,71,72], it is unclear if all geometries proposed in the L-state crystal structures [5][6][7][8][9] are indeed sampled during the reaction path. The significant energy barrier for retinal isomerisation from 15-trans to 15-syn [32,46] makes it unlikely that a 13-cis, 15-syn geometry [8] could be reached during the K-to-L transition [33].…”

“…[37] based on the QM computations from Refs. [38,39]. In QM/MM computations we used the all-atom parameter set [36] for the aromatic side-chains and the extended atom representation [40] for the remaining groups, or the allatom parameter set [36] for the entire system.…”

Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

“…The most characteristic resonances of PAMAM in G3 4transRet and the other bioconjugates obtained here are those of two methylene group protons, H-20 and H-21 (for atom numbering see Figure 1), seen at 3.70 and 3.51 ppm, respectively. The broad resonance at 8.2 ppm (lower spectrum) belongs to the internal N-H protons of the PAMAM dendrimer, which slowly undergoes substitution with the deuterium solvent and eventually disappears, and hence is not present in the upper spectrum for the bioconjugate mixture which was recorded after 12 hours of incubation of initial simulation 30 and dynamic simulation 31 show that lowest energy configuration is all-trans, which is about 2.1 kcal/mol lower than that of 13-cis. Moreover, the flexibility induced by the polyene chain of retinal in the bacteriorhodopsin-retinal Schiff base might be responsible for enabling the cis-trans transition and modifying the pK a of the retinal-protonated Schiff base in bacteriorhodopsin. )…”