(616f) The Effect of Interactions with Silica Surface On the Conformation of Antimicrobial Peptide Cecropin P1 Using Molecular Dynamics Simulation

Cecropin P1 is a 31 amino acid peptide found in nematodes from the stomachs of pigs which exhibits antimicrobial activity predominantly against Gram-negative bacteria (with reduced activity against Gram-positive bacteria) through pore formation in cell membrane as a result of its alpha helical structure. An analog of Cecropin P1, known as Cecropin P1 C, where a cysteine residue is attached at the C terminal, is also selected as a model peptide because of a cysteine residue is necessary for the peptides to be attached on a solid surface. It is of interest to relate the loss of antimicrobial activity (if any) as a result of attachment of these peptides to a surface to the conformational changes.

A Molecular Dynamics simulation was performed using AMBER to calculate the secondary structure, potential energy and end-to-end distance for Cecropin P1 and Cecropin P1 C in solution as well as for Cecropin P1 C physically adsorbed onto silica surface or anchored to the surface with a linker molecule. The simulation results showed an equilibrium structure consisting of two α helix regions for Cecropin P1 as well as for Cecropin P1 C with a sharp bend for the latter. Eventhough this could not be compared with NMR structure, the prediction of two α helical regions is consistent with the available structures of other antimicrobial peptides. % α helix of the equilibrium structure is highest (40%) for Cecropin P1 in the presence of 0.12M salt as a result of shielding of electrostatic interactions, followed by Cecropin P1 C (30%) and Cecropin P1 (25%). The conformation of adsorbed Cecropin P1 C on silica surface indicated a α helix content of around 10% as opposed to a value of around 30% in solution. In addition, the adsorbed Cecropin P1 C on silica surface does not exhibit a hairpin bend with the end to end distance being around 4 nm compared to a value of 1.5 to 2 nm in solution. The α helix content and end to end distance of Cecropin P1 C anchored to the silica surface with oligo ethylene oxide spacer molecule were found to be significantly different from those for adsorbed polypeptide.