title: Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus.
abstract: Using a combination of coarse-grained and atomistic molecular dynamics simulations we have investigated the membrane binding and folding properties of the membrane lytic peptide of Flock House virus (FHV). FHV is an animal virus and an excellent model system for studying cell entry mechanisms in non-enveloped viruses. FHV undergoes a maturation event where the 44 C-terminal amino acids are cleaved from the major capsid protein, forming the membrane lytic (γ) peptides. Under acidic conditions, γ is released from the capsid interior allowing the peptides to bind and disrupt membranes. The first 21 N-terminal residues of γ, termed γ1, have been resolved in the FHV capsid structure and γ1has been the subject of in vitro studies. γ1is structurally dynamic as it adopts helical secondary structure inside the capsid and on membranes, but it is disordered in solution. In vitro studies have shown the binding free energies to POPC or POPG membranes are nearly equivalent, but binding to POPC is enthalpically driven, while POPG binding is entropically driven. Through coarse-grained and multiple microsecond all-atom simulations the membrane binding and folding properties of γ1are investigated against homogeneous and heterogeneous bilayers to elucidate the dependence of the microenvironment on the structural properties of γ1. Our studies provide a rationale for the thermodynamic data and suggest binding of γ1to POPG bilayers occurs in a disordered state, but γ1must adopt a helical conformation when binding POPC bilayers.
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Shivangi
authors.initials: S
authors.lastname: Nangia
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, United States. Electronic address: eric.may@uconn.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: May
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D030381:Nodaviridae / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D014764:Viral Proteins
keywords: Anti-microbial peptides; Bilayers; Coarse-grained simulations; Molecular dynamics simulations; Virus infection