The dielectric effect of the environment on the pK(a) of the retinal Schiff base and on the stabilization of the ion pair in bacteriorhodopsin

We have performed DFT calculations, using the DMOL implementation of the COSMO (Conductor like Solvent Model), to investigate the effect of different dielectric responses of the environment on the structure, electronic configuration and proton affinity (PA) of a series of conjugated Schiff base models. The studied molecules include conjugated Schiff base models containing different number of double bonds and methyl substitution(s), as well as the complete structure of the retinal Schiff base. The COSMO implementation of the DMOL package program was used to implicitly simulate the solvent effects. The calculations were performed using different dielectric constants, in order to simulate gas phase (ε = 1.0), protein environment (ε = 4.0) and the aqueous solution (ε = 78.4). The effect of the solvent model on the geometry and the PA of a series of conjugated Schiff base structure has been studied. Simulating the environment as a continuum model suggests that the protein environment may, very efficiently, adjust the pK(a) of the chromophore by modifying local screening effects in the vicinity of the retinal Schiff base and, in this way, control the process of the proton transfer. The results show that slightly modifying the dielectric response of the microenvironment can significantly influence the protonation state of the Schiff base group. Comparison of the PA of the retinal Schiff base and a model for the aspartate side chain shows that the ion pair cannot be found stable within gas phase calculations. Considering the environment in the form of a continuum model significantly influences the potential energy surface of the proton transfer between a protonated Schiff base group and the aspartate side chain. In gas phase calculations, the calculated PA of the aspartate group is much larger than that of the studied model Schiff bases. After inclusion of the solvent model in the calculations, the PA of the retinal Schiff base and aspartic acid become very close to each other. The explicit inclusion of the protein environment, however, seems to be essential for obtaining a stable ion pair. Without inclusion of further stabilization effects, for example explicit consideration of the monopole/dipole effects of the environment and/or inclusion of implicit solvent models, one cannot approach any stable ion pair of the protonated Schiff base group and negatively charged aspartate, which is believed to exist in bacteriorhodopsin (bR) as the starting configuration before the photocycle. With this respect, the effect of water molecules is also discussed. (C) 2000 Elsevier Science B.V.