500 picosecond molecular dynamics simulation of amphiphilic polypeptide Ac(LKKL)4 NHEt with 1,2 di-mysristoyl-sn-glycero-3-phosphorylcholine (DMPC) molecules.

ABSTRACT

Molecular dynamics (MD) simulation of the interaction between amphiphilic polypeptide Ac(LKKL)4NHEt and 4 DMPC (1,2 di-mysristoyl-sn-glycero-3-phosphorylcholine) molecules has been carried out at 310 K for 500 picoseconds (ps) using AMBER 4.0. Interaction energy and a number of conformational parameters are calculated for the subaveraged coordinates, using P-CURVES 3.1 and our MD trajectory analysis program ANALMD. No significant change in DMPC headgroup conformation was observed. However, the mobility of P atoms was found to be restricted. The chains were quite flexible and their flexibility increased towards the ends. They interacted amongst themselves. The polypeptide remained predominantly in alpha-helical conformation. Leu1 and Lys2 at the N terminus and Leu13 to Leu16 at C terminus assumed non helical conformation and were quite flexible. Average interaction energy between the polypeptide and DMPC molecules was found to be -151.828 kcal*mol-1. The main contributory factor was electrostatic interaction of Lys NH3+ groups with the DMPC phosphates. On an average one Lys chain interacted with 1.5 DMPC molecules. Central region of the polypeptide had better contact with DMPC molecules. A model for the fusogenic properties of the polypeptide is presented on the basis of MD results.