Investigation of the interactions between Melittin and the PLGA and PLA polymers: molecular dynamic simulation and binding free energy calculation

Nanobiotechnology is the application of nanotechnology in nanomedicine. Recently, the use of antimicrobial peptides as a substitute for antibiotics and anticancer drugs has attracted increasing attention. Therefore, the study of the structural behavior of these peptides such as Melittin and their interactions with biocompatible and biodegradable polymers is important. This study was performed to evaluate the critical interactions in the formation of the Melittin-polymers complexes. The aim of the current study was to investigate molecular mechanisms of Melittin encapsulation in biopolymers by molecular dynamics (MD) simulation. The results indicated that the basic residues of Melittin could play crucial roles in the formation of the Melittin-polymer complexes. Our results also demonstrate that Melittin could make considerable hydrogen bonds with the carboxyl groups of PLA and PLGA polymers. The energy and RDF analyses showed that the van der Waals, hydrophobic, and electrostatic interactions were important in the Melittin adsorption on the polymer aggregations. The simulation results also reveal that although the Melittin conformation was stable in the polymer systems, PLGA could stabilize the Melittin structure more than the PLA. To gain molecular insights into the contributions of each Melittin residue to the interactions of the peptide with the mentioned polymers, eleven independent 200 ns all-atom MD simulations were performed for each peptide-polymer system.