Effects of electric field on alamethicin bound at the lipid-water interface: a molecular mechanics study

• Published in: Biophysical journal Vol. 65; no. 2; pp. 608 - 617
• Main Authors: Galaktionov, S.G., Marshall, G.R.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.08.1993; Biophysical Society
• Subjects: Alamethicin - chemistry; Binding Sites; Biological and medical sciences; Conformational dynamics in molecular biology; Electrochemistry; Fundamental and applied biological sciences. Psychology; Lipids; Mathematics; Membrane Potentials; Models, Theoretical; Molecular biophysics; Protein Conformation; Protein Structure, Secondary; Water; Molecular interaction; Artificial membrane; Electric field effect; Structure function relationship; Conformational dynamics
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(93)81093-2

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.