Paper Citing NAMD - Abstract
Munteanu, Cristian V. A.; Alexandru, Petruta; Spiridon, Laurentiu N.; Petrescu, Andrei-Jose; Milac, Adina-Luminita
INSIGHTS INTO CECROPIN-MEMBRANE INTERACTION MECHANISM GIVEN BY MOLECULAR DYNAMICS SIMULATIONS
Romanian Journal of Biochemistry, 49:21-31, JAN-JUN 2012
Cancer is a leading cause of death worldwide and conventional chemotherapeutic treatments are not always effective, induce resistance and are often associated with serious side effects. Cationic antimicrobial peptides (AMPs) represent a promising alternative to conventional anticancer drugs due to their selectivity for malignant cells and their non-toxic properties. One such class of peptides is cecropins, initially identified in insects but later isolated also from mammalian tissues. Although electrostatic attraction between the negatively charged cancer cells and the positively charged AMPs is believed to play a major role in the strong binding and selective disruption of bacterial and cancer cell membranes, the exact mechanism of action has not been elucidated yet. Using these peptides as therapeutic agents requires a detailed understanding of their mechanisms of action. Our goal is to better understand the interaction between cecropin P and membrane using molecular dynamics simulations (20ns simulation time) of atomically detailed models of cecropin P in interaction with POPE lipid bilayer. We built three different systems, in which the cecropin helix is initially oriented parallel with the lipid bilayer. In the first two systems electrostatic interactions are favoured, since peptide helix is oriented with positive charges facing negatively charged lipid phosphate groups and the distance between helix axis and phosphate plane is 9A and 6A, respectively. In the third system, hydrophobic interactions are favoured, cecropin helix is partially buried in the membrane bilayer, with the apolar side interacting with hydrophobic lipid tails and the cationic face interacting with phosphate groups. Our results indicate a lower stability of the first two systems, based on electrostatic interactions, while the system in which hydrophobic interactions dominate is highly stable and peptide induces deformations of the lipid bilayer. These results suggest that the hydrophobic characteristics of the peptide may be used to facilitate peptide penetration in the membrane.
