Adsorption of folic acid molecule on diphenylalanine peptide nanohole as a drug delivery in cancer treatment: a molecular dynamics simulation study

Abstract

Context: Using the molecular dynamics simulation method, the adsorption of folic acid as a drug with diphenylalanine peptide nanohole as an efficient nanodrug delivery system was investigated computationally. It focuses on the structural properties, drug loading capacity in the carrier, intermolecular interactions, and drug encapsulation behaviors. The results show that the average number of hydrogen bonds between diphenylalanine and folic acid will increase when the system reaches equilibrium. In addition, by increasing the weight concentration of folic acid from 0.3 to 0.9%, the number of hydrogen bond between them increases about 18%. In other words, hydrogen bonding can play an effective role in the binding of folic acid to the drug carrier. The results of the radial distribution function of water molecules around the carrier mass center show that its effective radius is around 1.2 nm (or 12 Å), which is in a good agreement with the results obtained from the hydrodynamic radius.

Method: The initial structures were optimized in Amber molecular mechanics using Gaussian 09 software in aqueous medium in DFT/B3LYP/6-31 g(d). The molecular structure of folic acid was obtained from the PubChem database. The initial parameters are embedded in AmberTools. To calculate partial charges, restrained electrostatic potential (RESP) method was used. Gromacs 2021 software, modified water model (SPC/E), and Amber 03 force field have been used in all simulations. VMD software was used to view simulation photos.

Keywords: Anticancer; Drug delivery; Folic acid; Molecular dynamics; Peptide nanohole.