Molecular dynamic simulation of Buforin IIb anticancer peptide with POPC-Cholesterol model membrane

The multidrug resistance process has hindered the effect of chemotherapeutics. Demands for the design and synthesis of novel therapeutic peptides are increasing. Recent studies have shown the anticancer activity of Buforin IIb against ۶۲ cancer cell lines . It is a ۲۱-mer peptide (RAGLQFPVGRLLRRLLRRLLR) and has a remarkable selectivity toward different cancer cell lines. It has been indicated that the anticancer action of Buforin IIb involves the induction of cancer cell apoptosis. However, the mechanism of anticancer activity remains unclear . During this study, the interaction of Buforin IIb with the model bilayer (POPC-CHOL) was analyzed with All-atom molecular dynamic simulations. The model bilayer was constructed with Charmm-GUI membrane builder tool, and after ۵۰۰ps equilibration at ۳۱۰.۱۵ ◦K, the motion of Buforin IIb on the upper leaflet surface area was investigated during ۱۰۰ns of atomistic simulation by GROMACS ۲۰۱۸.۱ software. RMSD analysis indicates the stable secondary structure of Buforin IIb at the vicinity of the bilayer. In such a case, the energy calculations examined the details of the interaction at the peptide-bilayer interface. The distance profile between the peptide center of mass and headgroups of the bilayer confirmed the adsorption of Buforin IIb on the membrane surface. These results also demonstrated the key effect of Proline residue at the adsorption state. Totally, this simulation unraveled the initial penetrating process of Buforin IIb through a rigid bilayer (POPCCHOL), which could be informative for understanding the mechanistic features of peptide anticancer activity.

کلیدواژه ها:

Anticancer ، Buforin IIb ، Molecular dynamic simulations