SECONDARY STRUCTURE OF AN ISOLATED P-REGION FROM THE VOLTAGE-GATED SODIUM-CHANNEL - A MOLECULAR MODELING DYNAMICS STUDY

Conformational studies of synthetic peptides corresponding to the pore -forming regions of voltage-gated sodium channels show a high tendency for beta-sheet conformation when interacting with lipid vesicles, as revealed by circular dichroism and infrared spectroscopy. These observ ations have guided our choice of possible molecular models for the P-r egion peptide of domain II of voltage-gated sodium channels: three alt ernative beta-hairpins, with differing turn assignments, or an alpha-h elical hairpin. After generation of models by distance geometry-based methods, molecular dynamics (MD) simulations were run, in the absence of explicit solvent molecules but employing three different dielectric constants, to explore possible conformational preferences. The simula tions in the different dielectric environments suggest that a 4-residu e turn with the sequence LCGE yields more stable beta-hairpins. The MD results suggest that the SS1 part of the peptide may be more stable a s an alpha-helix, whereas the SS2 part tends to adopt a beta-conformat ion. (C) 1997 Elsevier Science B.V.