Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics

Abstract

Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

Molecular dynamics simulations of potassium channels

“…[165,166]), MD simulations have been extended to increasingly complex membrane proteins [167][168][169][170]. These simulations are able to provide insights into the nature of the interactions between membrane proteins and their lipid environment [168,[171][172][173][174] and analysis of those crystal structures of membrane proteins that contain lipids provides a detailed structural per-spective on lipid/protein interactions [56,175]. A number of experimental studies have also revealed the importance of bound lipid molecules for the stability and function of some membrane proteins [176][177][178][179][180] For example, in the case of the K + channel KcsA, acidic phospholipids appear to bind to specific (non-annular) sites at which they play a role in refolding and possibly in function [181][182][183].…”

Domain Formation in Phosphatidylcholine Bilayers Containing Transmembrane Peptides: Specific Effects of Flanking Residues

“…Especially tryptophans and tyrosines are abundant in the interface, and they are generally thought to have an anchoring (4,5) and stabilizing (6,7) function. Moreover, it has been suggested that aromatic residues are essential for the proper folding and assembly (8), and functioning of integral membrane proteins (9,10).…”

Computational Study of Cytolytic Peptides: Monomeric-Oligomeric Structures and Ligand Interactions

“…The NMR structure was obtained in solution and does not provide any information regarding lipid molecules around the peptide. Our method closely follows a previous method, which has been successfully applied to gramicidin, 18 alpha helical systems, 19,20 rhodopsin, 21 bacteriorhodopsin, 22 and fusion domain of influenza hemagglutinin (HA). 23 Constant membrane surface area is maintained, with constant normal pressure applied in the direction perpendicular to the membrane to adequately maintain constant surface tension of the lipid bilayer throughout the simulation.…”