MOLECULAR-DYNAMICS STUDIES OF BACTERIORHODOPSINS PHOTOCYCLES

The availability of the structure of bacteriorhodopsin from electron m icroscopy studies has opened up the possibility of exploring the proto n pump mechanism of this protein by means of molecular dynamics simula tions. In this review we summarize earlier theoretical investigations of the photocycle of bacteriorhodopsin including relevant quantum chem istry studies of retinal, structure refinement, molecular dynamics sim ulations, and evaluation of pK(a) values. We then review a series of r ecent modeling efforts which refined the structure of bacteriorhodopsi n adding internal water, and which studied the nature of the J interme diate and the likely geometry of the K-590 and L(550) intermediates (s trongly distorted 13-cis) as well as the sequence of retinal geometry and protein conformational transitions which are conventionally summar ized as the M(412) intermediate. We also review simulations of the pho tocycle of light-adapted bacteriorhodopsin at T=77 K and of the photoc ycle of dark-adapted bacteriorhodopsin, both cycles differing from the conventional photocycle through a nonfunctional (pure 13-cis) retinal geometry of the corresponding K-590 and L(550) states. The simulation s demonstrate a potentially critical role of water and of minute reori entations of retinal's Schiff base nitrogen in controlling proton pump ing in bR(568); the simulations also indicate the existence of heterog eneous photocycles. The results exemplify the important role of molecu lar dynamics simulations in extending investigations on bacteriorhodop sin to a level of detail which is presently beyond experimental resolu tion, but which needs to be known to resolve the pump mechanism of bac teriorhodopsin. Finally, we outline the major existing challenges in t he field of bacteriorhodopsin modeling.