Understanding the energetics of helical peptide orientation in membranes

Durba Sengupta, Lars Meinhold, Dieter Langosch, G. Matthias Ullmann, Jeremy C. Smith

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Understanding the energetic factors determining the positioning and orientation of single-helical peptides in membranes is of fundamental interest in structural biology. Here, a simple 5-slab continuum dielectric model for the membrane is examined that distinguishes between the solvent, headgroup, and core regions. An analytical solution for the electrostatic solvation of a single dipole and an all-atom model of N-methylacetamide are used to demonstrate the effect of the dielectric boundaries in the system on peptide dipole orientation. The dipole orientation energy is shown to dominate the electrostatic solvation energy of a polyalanine helix in the membrane. With an additional surface-area-dependent term to account for the cavity formation in the aqueous region, the continuum electrostatics description is used to examine several helical peptides, the atoms of which are explicitly represented with a molecular mechanics force field. The experimentally determined tilt angles of a number of peptides of alternating alanine and leucine residues, and of glycophorin and melittin, are accurately reproduced by the model. The factors determining the tilt angles and their fluctuations are analyzed. The tilt angles of the simpler peptides are found to increase approximately linearly with peptide length; this effect is also rationalized. The analysis and model presented here provide a step toward the prediction of helical membrane protein structure.

Original languageEnglish
Pages (from-to)913-922
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Volume58
Issue number4
DOIs
StatePublished - 1 Mar 2005

Keywords

  • Dipole
  • Glycophorin
  • Melittin
  • Membrane helices
  • Poisson-Boltzmann equation
  • Polyalanine
  • Tilt angle fluctuation
  • WALP

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