Characterization of proline-containing alpha-helix (helix F model of bacteriorhodopsin) by molecular dynamics studies

Abstract

Many of the bilayer spanning segments of membrane transport proteins contain proline residues, and most of them are believed to occur in alpha-helical form. A proline residue in the middle of an alpha-helix is known to produce a bend in the helix, and recent studies have focused on characterizing such a bend at atomic level. In the present case, molecular dynamics (MD) studies are carried out on helix F model of bacteriorhodopsin (BR) Ace-(Ala)7-Trp-(Ala)2-Tyr-Pro-(Ala)2-Trp- (Ala)8-NHMe and compared with Ace-(Ala)7-Trp-(Ala)2-Tyr-(Ala)3-Trp-(Ala)8-NHMe in which the proline is replaced by alanine. The bend in the helix is characterized by structural parameters such as kink angle (alpha), wobble angle (theta), virtual torsion angle (rho), and the hydrogen bond distance d (Op-3 ... Np+1). The average values and the flexibility involved in these parameters are evaluated. The correlation among the bend related parameters are estimated. The equilibrium side chain orientations of tryptophan and tyrosine residues are discussed and compared with those found in the recently proposed model of bacteriorhodopsin. Finally, a detailed characterization of the bend in terms of secondary structures such as alpha I, alpha II and goniometric helices are discussed, which can be useful in the interpretation of the experimental results on the secondary structures of membrane proteins involving the proline residue.