Investigation of antibacterial activity of cathelicidin using molecular dynamics simulation

Antimicrobial peptides (AMPs) are essential components of innate immunity system that can be found in most living organisms. These small cationic peptides have indicated direct antimicrobial activity against various microorganisms such as bacteria, viruses, fungi and parasites [1].Nowadays AMPs are so important because they have been considered as potential replacement agents to conventional antibiotics due to their rarely antimicrobial resistance [2].One well-known AMP is Cathelicidin which is expressed in epithelial cells and in leukocytes such as monocytes, neutrophils, T cells, NK cells, and B cells. Cathelicidin is small, cationic peptide that possesses broad-spectrum antimicrobial activity. LL-37, the only human cathelicidin, is a 37-residue, amphipathic, helical and cationic (+6) peptide[3].Membrane insertion of small peptides plays important roles in antimicrobial defense. Molecular dynamics simulation technique is a useful tool to investigate this insertion. In this study, we tried to investigate the interactions between LL-37 and dipalmitoylphosphatidylcholine (DPPC) bilayer by use of Umbrella sampling (US) simulations. Our results showed that by pulling the peptide closer to the membrane, the PMF (potential of the mean force) and the free energy decreases with a remarkable value that is about 5KBT. Therefore comparing this energy difference with thermal flactuation (kBT) we can conclude that LL-37 has a remarkable tendency to the membrane. In the following we are going to work on finding other parameters which are effective on antibacterial activity of cathelicidin like, the optimum direction and number of peptides.

Keywords:

Antimicrobial peptides , Cathelicidin , Host defense peptide , DPPC , LL-37