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

dWe have performed DFT calculations, using the DMOL implementation of the C OSMO (Conductor like Solvent Model), to investigate the effect of different dielectric responses of the environment on the structure, electronic confi guration and proton affinity (PA) of a series of conjugated Schiff base mod els. The studied molecules include conjugated Schiff base models containing different number of double bonds and methyl substitution(s), as well as th e complete structure of the retinal Schiff base. The COSMO implementation o f the DMOL package program was used to implicitly simulate the solvent effe cts. The calculations were performed using different dielectric constants, in order to simulate gas phase (epsilon = 1.0), protein environment (epsilo n = 4.0) and the aqueous solution (epsilon = 78.4), The effect of the solve nt model on the geometry and the PA of a series of conjugated Schiff base s tructure 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 pro ton transfer. The results show that slightly modifying the dielectric respo nse of the microenvironment can significantly influence the protonation sta te of the Schiff base group. Comparison of the PA of the retinal Schiff bas e and a model for the aspartate side chain shows that the ion pair cannot b e found stable within gas phase calculations. Considering the environment i n the form of a continuum model significantly influences the potential ener gy surface of the proton transfer between a protonated Schiff base group an d 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 b ases. After inclusion of the solvent model in the calculations, the PA of t he retinal Schiff base and aspartic acid become very close to each other. T he explicit inclusion of the protein environment, however, seems to be esse ntial for obtaining a stable ion pair. Without inclusion of further stabili zation effects, for example explicit consideration of the monopole/dipole e ffects 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 bacteriorhodop sin (bR) as the starting configuration before the photocycle. With this res pect, the effect of water molecules is also discussed. (C) 2000 Elsevier Sc ience B.V. All rights reserved.