Mechanism of the unfolding of transmembrane α-helical segment (1-36)-bacteriorhodopsin studied by molecular dynamics simulations

The unfolding of the first transmembrane segment 1-36 bacteriorhodopsin (BR) was studied using 1.25 ns molecular dynamics (MD) simulation with an explicit representation of chloroform/methanol 1:1 mixture and a series of long (from 10 to 60 ns) Langevin dynamics (LD) simulations. Comparison of MD and LD simulations shows that the random and frictional forces of Langevin equation provides a good model for the weakly polar chloroform/methanol mixture. The dielectric permeability ε_o = 1-2 (ε = ε_or) was found to be suitable for the modeling of the shielding effect of a weakly polar solvent in the LD simulations. The enhancement of short-range electrostatic interactions stabilizes the α-helix in LD simulations. The α-helix unfolding proceeds through the formation of local regions, stabilized by π-helical hydrogen bonds (π-bulges), in the central part of (1-36)-BR. Being formed, the π-bulges can propagate to metastable structures with partially solvated backbone intermediates on the way to an α-helix-random coil transition. Two regions of the π-bulges formation within (1-36)-BR are attached to the Leu-Gly-Thr sequence.