Biomaterial Database

Simulation of voltage-dependent interactions of alpha-helical peptides with lipid bilayers. 1996

P C Biggin, and M S Sansom

Laboratory of Molecular Biophysics, University of Oxford, UK.

Pore formation in lipid bilayers by channel-forming peptides and toxins is thought to follow voltage-dependent insertion of amphipathic alpha-helices into lipid bilayers. We have developed an approximate potential for use within the CHARMm molecular mechanics program which enables one to simulate voltage-dependent interaction of such helices with a lipid bilayer. Two classes of helical peptides which interact with lipid bilayers have been studied: (a) delta-toxin, a 26 residue channel-forming peptide from Staphylococcus aureus; and (b) synthetic peptides corresponding to the alpha 5 and alpha 7 helices of the pore-forming domain of Bacillus thuringiensis CryIIIA delta-endotoxin. Analysis of delta-toxin molecular dynamics (MD) simulations suggested that the presence of a transbilayer voltage stabilized the inserted location of delta-toxin helices, but did not cause insertion per se. A series of simulations for the alpha 5 and alpha 7 peptides revealed dynamic switching of the alpha 5 helix between a membrane-associated and a membrane-inserted state in response to a transbilayer voltage. In contrast the alpha 7 helix did not exhibit such switching but instead retained a membrane associated state. These results are in agreement with recent experimental studies of the interactions of synthetic alpha 5 and alpha 7 peptides with lipid bilayers.

UI	MeSH Term	Description	Entries
D008051	Lipid Bilayers	Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.	Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D004563	Electrochemistry	The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.	Electrochemistries
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001427	Bacterial Toxins	Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.	Bacterial Toxin,Toxins, Bacterial,Toxin, Bacterial
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D017433	Protein Structure, Secondary	The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation.	Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein