title: Spontaneous membrane-translocating peptide adsorption at silica surfaces: a molecular dynamics study.
abstract: Spontaneous membrane-translocating peptides (SMTPs) have recently been shown to directly penetrate cell membranes. Adsorption of a SMTP, and some engineered extensions, at model silica surfaces is studied herein using fully atomistic molecular dynamics simulations in order to assess their potential to construct novel drug delivery systems. The simulations are designed to reproduce the electric fields above single, siloxide-rich charged surfaces, and the trajectories indicate that the main driving force for adsorption is electrostatic. An increase in the salt concentration slows down but does not prevent adsorption of the SMTP to the surface; it also does not result in peptide desorption, suggesting additional binding via hydrophobic forces. The results are used to design extensions to the peptide sequence which we find enhance adsorption but do not affect the adsorbed conformation. We also investigate the effect of surface hydroxylation on the peptide adsorption. In all cases, the final adsorbed conformations are with the peptide flattened to the surface with arginine residues, which are key to the peptide's function, anchoring it to the surface so that they are not exposed to solution. This conformation could impact their role in membrane translocation and thus has important implications for the design of future drug delivery vehicles.
authors.affiliation: Department of Chemical and Process Engineering, University of Strathclyde , James Weir Building, 75 Montrose Street, Glasgow G1 1XJ, United Kingdom.
authors.forename: Karina
authors.initials: K
authors.lastname: Kubiak-Ossowska
authors.forename: Glenn
authors.initials: G
authors.lastname: Burley
authors.forename: Siddharth V
authors.initials: SV
authors.lastname: Patwardhan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Mulheran
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D010455:Peptides; D012822:Silicon Dioxide