Modeling of Peptides and proteins in membrane environment. I. A solvation model mimicking a lipid bilayer

A theoretical solvation model: of peptides and proteins Chat mimics the het erogeneous membrane-water. system was proposed. Our approach is based on th e, combined use of atomic parameters of solvation for water and hydrocarbon s, which approximates the hydrated polar groups and acyl chains of lipids, respectively. This model was tested in simulations of several peptides: a n onpolar 20-mer polyleucine, a hydrophobic peptide with terminal polar group s, and a strongly amphiphilic peptide. The conformational space of the pept ides in the presence of the membrane was studied by the Monte Carlo method. Unlike a polar solvent and vacuum, the membrane-like environment was shown to stabilize the alpha-helical conformation: low-energy structures have a helicity index of 100% in all eases. At the same time, the energetically mo st favorable orientations of the peptides relative to the membrane depend o n their hydrophobic properties: nonpolar polyleucine is entirely immersed i n the bilayer and. the hydrophobic peptide with polar groups at the termini adopts a transbilayer orientation whereas the amphiphilic peptide lies at the int interface parallel to the membrane plane. The results of the simula tions agree well with the available experimental data for these systems. In the following communications of this series, we plan to describe applicati ons of the solvation model to membrane-bound proteins and peptides with bio logically important functional activities.