Modeling of peptides and proteins in a membrane environment. II. Structural and energetic aspects of glycophorin A in a lipid bilayer

The conformational space of a hydrophobic peptide fragment of glycophorin A in a lipid membrane was studied with the Monte Carlo method using the solv ation model described in the first communication of this series, The simula tion was performed for various starting orientations of the peptide relativ e to the membrane bilayer: outside. inside, partially immersed, and transbi layer. We showed that the membrane substantially stabilizes the alpha-helic al conformation of the central hydrophobic part of the glycophorin A molecu le, which for the most part is immersed in the apolar core of the bilayer. For various conformational stales, energy values were calculated and the or ientations of the peptide relative to the membrane were characterized. Depe nding on the thick-ness of the bilayer. either an entirely alpha-helical co nformation in transbilayer orientation or a conformation with a kink in the central part of the helix with the N- and C-termini exposed on one side of the membrane corresponds to the minimal-energy structure. The transmembran e orientation of glycophorin A is energetically advantageous when the membr ane thickness is close to the length of its hydrophobic helical portion, wh ich is consistent with the effect of "hydrophobic match" observed experimen tally. The prospects for further refinement of the model are discussed.