title: Effects of electric field on alamethicin bound at the lipid-water interface: a molecular mechanics study.
abstract: A systematic molecular mechanics study of the alamethicin molecule was made to determine a set of low-energy conformers in vacuo and in aqueous environment. The behavior of these conformers was investigated at the phase boundary which was modeled as a plane dividing two compartments with solvation properties of water and octanol with a constant electric field applied normal to the boundary. The calculations were performed with a molecular mechanics program for calculation of stable conformations at the phase boundary utilizing the Empiric Conformational Energy Program for Peptides force field and the Hopfinger-Scheraga solvation model. 371 minimum energy conformers of alamethicin, determined in vacuo with the build-up procedure, were used as starting conformations for energy minimization in aqueous environment and at the phase boundary. Only 49 interphase-bound structures were within 12 kcal/mol of the minima which was found. No helical structures having values close to the canonical parameters for an alpha- or 3(10)-helix were found despite the presence of eight alpha-methylalanine residues which favor the formation of these helices; four helix-like structures were found, having all negative phi, psi values. All the helical conformers have very high energies in water (approximately 14 kcal/mol), but are quite stable at the phase boundary (3.7-6.8 kcal/mol above the lowest minima found). The implications of these results for proposed mechanisms for membrane-binding and voltage-dependent gating are considered.
authors.affiliation: Center for Molecular Design Washington University, St. Louis, MO 63130.
authors.forename: S G
authors.initials: SG
authors.lastname: Galaktionov
authors.forename: G R
authors.initials: GR
authors.lastname: Marshall
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D001665:Binding Sites; D004563:Electrochemistry; D008055:Lipids; D008433:Mathematics; D008564:Membrane Potentials; D008962:Models, Theoretical; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014867:Water
chemical_list: D008055:Lipids; D014867:Water; D000408:Alamethicin