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Interactions of lipids and detergents with a viral ion channel protein: molecular dynamics simulation studies.

ABSTRACT: Structural studies of membrane proteins have highlighted the likely influence of membrane mimetic environments (i.e., lipid bilayers versus detergent micelles) on the conformation and dynamics of small ?-helical membrane proteins. We have used molecular dynamics simulations to compare the conformational dynamics of BM2 (a small ?-helical protein from the membrane of influenza B) in a model phospholipid bilayer environment with its behavior in protein-detergent complexes with either the zwitterionic detergent dihexanoylphosphatidylcholine (DHPC) or the nonionic detergent dodecylmaltoside (DDM). We find that DDM more closely resembles the lipid bilayer in terms of its interaction with the protein, while the short-tailed DHPC molecule forms "nonphysiological" interactions with the protein termini. We find that the intrinsic micelle properties of each detergent are conserved upon formation of the protein-detergent complex. This implies that simulations of detergent micelles may be used to help select optimal conditions for experimental studies of membrane proteins.

SUBMITTER: Rouse SL

PROVIDER: S-EPMC4306293 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Interactions of lipids and detergents with a viral ion channel protein: molecular dynamics simulation studies.

Rouse Sarah L SL Sansom Mark S P MS

The journal of physical chemistry. B 20141021 3

Structural studies of membrane proteins have highlighted the likely influence of membrane mimetic environments (i.e., lipid bilayers versus detergent micelles) on the conformation and dynamics of small α-helical membrane proteins. We have used molecular dynamics simulations to compare the conformational dynamics of BM2 (a small α-helical protein from the membrane of influenza B) in a model phospholipid bilayer environment with its behavior in protein-detergent complexes with either the zwitterio ...[more]

PMID: 25286030

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Project description:Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees ) of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10) helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.

Dataset Information

Interactions of lipids and detergents with a viral ion channel protein: molecular dynamics simulation studies.

Publications

Interactions of lipids and detergents with a viral ion channel protein: molecular dynamics simulation studies.

Similar Datasets

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