Effect of interaction with coesite silica on the conformation of Cecropin P1 using explicit solvent molecular dynamics simulation

Explicit solvent molecular dynamics (MD) simulation was carried out for the antimicrobial peptides (i) Cecropin P1 and C-terminus cysteine modified Cecropin P1 (Cecropin P1 C) in solution, (ii) Cecropin P1 and Cecropin P1 C adsorbed onto coesite -Si - O - and Si - O - H surfaces, and (iii) Cecropin P1 C tethered to coesite -Si - O - surface with either (PEO)(3) or (PEO)(6) linker. Low energy structures for Cecropin P1 and Cecropin P1 C in solution consists of two regions of high alpha helix probability with a sharp bend, consistent with the available structures of other antimicrobial peptides. The structure of Cecropin P1 C at low ionic strength of 0.02 M exhibits two regions of high alpha helix probability (residues AKKLEN and EGI) whereas at higher ionic strength of 0.12 M, the molecule was more compact and had three regions of higher alpha helix probability (residues TAKKLENSA, ISE, and AIQG) with an increase in alpha helical content from 15.6% to 18.7% as a result of shielding of electrostatic interactions. In the presence of Cecropin P1 C in the vicinity of -Si - O - surface, there is a shift in the location of two peaks in H - O - H density profile to larger distances (2.95 angstrom and 7.38 angstrom compared to 2.82 angstrom and 4.88 angstrom in the absence of peptide) with attenuated peak intensity. This attenuation is found to be more pronounced for the first peak. H-bond density profile in the vicinity of -Si - O - surface exhibited a single peak in the presence of Cecropin P1 C (at 2.9 angstrom) which was only slightly different from the profile in the absence of polypeptide (2.82 angstrom) thus indicating that Cecropin P1 C is not able to break the H-bond formed by the silica surface. The alpha helix probability for different residues of adsorbed Cecropin P1 C on -Si - O - surface is not significantly different from that of Cecropin P1 C in solution at low ionic strength of 0.02 M whereas there is a decrease in the probability in the second (residues ISE) and third (residues AIQG) alpha helical regions at higher ionic strength of 0.12 M. Though the total alpha helical content of adsorbed and tethered Cecropin P1 C was lower for hydrophilic Si - O - H surface compared to hydrophobic -Si - O -, hydrophobicity of the surface did not significantly affect the alpha helix probability of different residues. The conformation of Cecropin P1 C in solution is closer to that of tethered to -Si - O - with (PEO)(6) than that tethered with (PEO)(3) as a result of less surface interaction of tethered polypeptide with a longer linker. At low ionic strength of 0.02 M, tethered Cecropin P1 C to -Si - O - is found to exhibit lower alpha helix (13.0%) compared to adsorbed (15.6%) for (PEO)(3) linker with this difference being insignificant for larger (PEO)(6) linker molecule. Experimental values of % alpha helix inferred from circular dichroism spectra of Cecropin P1 in solution as well as in adsorbed state on silica surface compared well with the corresponding values obtained from MD simulation thereby validating the simulation procedure. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4788662]