Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.
Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore MD, USA.
Charles H
CH
Chen
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore MD, USA.
Gregory
G
Wiedman
Wolfson Centre for Age Related Disorders, Kings College London, London, UK.
Ayesha
A
Khan
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore MD, USA. Electronic address: martin@ulmschneider.com.
Martin B
MB
Ulmschneider
D000042:Absorption; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding
D008051:Lipid Bilayers; D008555:Melitten
Bilayer; Circular dichroism; Melittin; Membrane; Molecular dynamics; Protein folding