Conformational changes of an antimicrobial peptide "Cecropin P1" on silica nanoparticles: Molecular dynamics and circular dichroism studies

Hector Chang, Purdue University

Abstract

Antimicrobial peptides (AMP) are innate mechanism of defense of the immune system found in insects and animals. It is shown that these peptides act against pathogenic bacteria, fungi, enveloped viruses, parasites and cancerous cells. They have the ability to penetrate the cell membrane, form pores which eventually lead to cell death. It is, therefore, important to characterize the secondary structure of AMP, important for its antimicrobial activity, under non polar environment such as lipid bilayer. It is also of interest to immobilize antimicrobial peptide (AMP) and their mimics onto surfaces such as packaging films. Immobilization of AMP may lead to partial or complete loss of their activity, due to random orientation and conformational changes. In order to fully retain their biological activity, AMP should be attached onto surfaces without affecting conformation. Our objective in this project is twofold, namely (i) to characterize the conformation of Cecropin P1 in the presence of a mixture of 2,2,2-triflouroethanol (TFE)/water of different composition and (ii) to investigate the conformational changes of Cecropin P1 (CP1) upon immobilization onto silica nanoparticles surface using molecular dynamics (MD) simulation and circular dichroism (CD). Explicit solvent MD simulation for TFE/water mixture indicated an increase in &agr; helical content with increasing TFE concentration from 12.9% (buffer) to 30.30% (15% TFE) consistent with experimental values (13.44% for buffer to 32.55% for 15% TFE) obtained from CD as a result of more intermolecular H-bond formation in nonpolar environment. Adsorption of CP1 onto silica was found to result in a decrease in &agr; helical content with increasing silica concentration (e.g. 32.55% in 15% TFE/water mixture to 30.02% and 28.83% in the same solution in the presence of 2.3% and 6.5% silica nanoparticles, respectively) with this effect being more pronounced for lower TFE concentrations. Explicit solvent MD simulation of five Cecropin P1 C molecules tethered to cosite silica with polyethylene oxide linker for two different peptide-peptide distances of separation (3 nm and 5 nm) indicated that the total &agr; helical content was lower for larger distance of separation as a result of reduced peptide-peptide interaction.

Degree

M.S.A.B.E.

Advisors

Narsimhan, Purdue University.

Subject Area

Biochemistry|Chemical engineering|Nanoscience

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