Next Article in Journal
Expression of an Organic Solvent Stable Lipase from Staphylococcus epidermidis AT2
Next Article in Special Issue
Recognition of Chiral Carboxylic Anions by Artificial Receptors
Previous Article in Journal
Synthesis and Characterization of a Heteroleptic Ru(II) Complex of Phenanthroline Containing Oligo-Anthracenyl Carboxylic Acid Moieties
Previous Article in Special Issue
Advances and Challenges in Protein-Ligand Docking
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2010, 11(9), 3177-3194;

Dimerization of Protegrin-1 in Different Environments

Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455-0132, USA
Author to whom correspondence should be addressed.
Received: 11 August 2010 / Revised: 24 August 2010 / Accepted: 3 September 2010 / Published: 9 September 2010
(This article belongs to the Special Issue Advances in Molecular Recognition)
Full-Text   |   PDF [1799 KB, uploaded 19 June 2014]


The dimerization of the cationic β-hairpin antimicrobial peptide protegrin-1 (PG1) is investigated in three different environments: water, the surface of a lipid bilayer membrane, and the core of the membrane. PG1 is known to kill bacteria by forming oligomeric membrane pores, which permeabilize the cells. PG1 dimers are found in two distinct, parallel and antiparallel, conformations, known as important intermediate structural units of the active pore oligomers. What is not clear is the sequence of events from PG1 monomers in solution to pores inside membranes. The step we focus on in this work is the dimerization of PG1. In particular, we are interested in determining where PG1 dimerization is most favorable. We use extensive molecular dynamics simulations to determine the potential of mean force as a function of distance between two PG1 monomers in the aqueous subphase, the surface of model lipid bilayers and the interior of these bilayers. We investigate the two known distinct modes of dimerization that result in either a parallel or an antiparallel β-sheet orientation. The model bilayer membranes are composed of anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) in a 1:3 ratio (POPG:POPE). We find the parallel PG1 dimer association to be more favorable than the antiparallel one in water and inside the membrane. However, we observe that the antiparallel PG1 β-sheet dimer conformation is somewhat more stable than the parallel dimer association at the surface of the membrane. We explore the role of hydrogen bonds and ionic bridges in peptide dimerization in the three environments. Detailed knowledge of how networks of ionic bridges and hydrogen bonds contribute to peptide stability is essential for the purpose of understanding the mechanism of action for membrane-active peptides as well as for designing peptides which can modulate membrane properties. The findings are suggestive of the dominant pathways leading from individual PG1 molecules in solution to functional pores in bacterial membranes. View Full-Text
Keywords: protegrin; potential of mean force; dimerization protegrin; potential of mean force; dimerization
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Vivcharuk, V.; Kaznessis, Y.N. Dimerization of Protegrin-1 in Different Environments. Int. J. Mol. Sci. 2010, 11, 3177-3194.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top