Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A computational method to calculate the orientation of membrane-associated alpha-helices with respect to a lipid bilayer has been developed. It is based on a previously derived implicit membrane representation, which was parameterized using the structures of 46 alpha-helical membrane proteins. The method is validated by comparison with an independent data set of six transmembrane and nine antimicrobial peptides of known structure and orientation. The minimum energy orientations of the transmembrane helices were found to be in good agreement with tilt and rotation angles known from solid-state NMR experiments. Analysis of the free-energy landscape found two types of minima for transmembrane peptides: i), Surface-bound configurations with the helix long axis parallel to the membrane, and ii), inserted configurations with the helix spanning the membrane in a perpendicular orientation. In all cases the inserted configuration also contained the global energy minimum. Repeating the calculations with a set of solution NMR structures showed that the membrane model correctly distinguishes native transmembrane from nonnative conformers. All antimicrobial peptides investigated were found to orient parallel and bind to the membrane surface, in agreement with experimental data. In all cases insertion into the membrane entailed a significant free-energy penalty. An analysis of the contributions of the individual residue types confirmed that hydrophobic residues are the main driving force behind membrane protein insertion, whereas polar, charged, and aromatic residues were found to be important for the correct orientation of the helix inside the membrane.

Original publication




Journal article


Biophys J

Publication Date





1650 - 1660


Antimicrobial Cationic Peptides, Computer Simulation, Lipid Bilayers, Magnetic Resonance Spectroscopy, Membrane Fluidity, Membrane Proteins, Models, Chemical, Models, Molecular, Protein Conformation