Quantum chemical and free energy simulation analysis of retinal conformational energetics

Ab initio quantum chemical and free energy molecular dynamics calculations are performed to examine energy differences between the all-trans and (13,15)cis conformers of retinal, i.e., those populated in the dark-adapted stale of bacteriorhodopsin. The quantum chemical results are used to derive an empirical force field that is used to calculate an adiabatic potential energy map for rotation about the bonds concerned. The same potential function is used in restrained molecular dynamics free energy calculations, with and without umbrella sampling. The simulation model yields a free energy of the (13,15)cis isomer similar to 2.1 kcal/mol higher than that of the all-trans species.