Simulation of erythrocyte membrane disruption by the anticancer peptide tritrpticin

According to the World Health Organization in ۲۰۲۰, the annual incidence of cancer has exceeded ۱۸ million patients. Cancer is predicted to be the number one cause of death in the world in the future. Efforts are made to discover an effective treatment with the aim of overcoming the drug resistance. The membrane disruptive peptides have been introduced as a new generation of receptor-independent drugs in the treatment of cancer. They are less likely to cause resistance, but they are toxic to normal cells and their structural properties should be modified. An essential prerequisite in this process is to understand the structure-function mechanism by simulating the molecular dynamics of a peptide–membrane system. Therefore, in this project, the role of the anti-cancer peptide, Tritrpticin, in disrupting the erythrocyte membrane was analyzed by molecular dynamics simulations. In this regard, both erythrocyte membrane with realistic lipids content and Tritrpticin (۱D۶X), were simulated for ۱۰۰ns with charmm۳۶ force field in a isothermal-isobaric ensemble (NPT) and target temperature of ۳۱۰.۱۵K°. For analyzing peptide-membrane interactions, the peptide structure was prepared at a distance of ۳ nm from the surface of the RBC membrane. Then the peptide-bilayer system, simulated for ۱۰۰ns in same NPT conditions. Analyzing kinetic and potential energy surfaces, charge density and roughness of bilayer surface and changes in peptide RMSD and RMSF contents, indicates tritrpticin affinity for disrupting erythrocyte membrane. These results are consistent with experimental studies of Arias et al. It is suggested to perform steered molecular dynamics simulations to evaluate the free energy between two components.

کلیدواژه ها:

Molecular dynamics ، Gromacs