Absorption of active pharmaceutical ingredients in a protein/lipid bilayer by dissipative particle dynamics

Abstract

Mesoscopic simulations are performed to study the absorption of eriodictyol and favipiravir for a charged protein inserted in a lipid bilayer. The dissipative particle dynamics (DPD) force field parameters of both compounds are obtained to approximate the experimental solubility in water. The lipid bilayer has 6 hydrocarbon tail beads and a head group. Electrostatic interactions are treated by Ewald sums with charge distributions to avoid the formation of ion pairs. The helical structure of the protein is maintained by using a harmonic potential on the dihedral angles of the backbone beads. The potential is successfully applied to an α-helix 1L4X and lysozime proteins. The calculated radius of gyration of lysozime is around 1.6 nm compared to ∼1.5 nm reported by Vaiwala et al. [Soft Matter, 17 (42), 9772–9785 (2021). doi:10.1039/D1SM01194D] who used a slightly different approach to maintain the helical structure. A charged lysozyme-type protein is used as a model within the lipid bilayer and it is in contact with water on both sides of the bilayer. The active ingredients without protein are found at the interface of the lipid bilayer but their concentration decreases when the protein is included because some of them diffuse to the interior of the protein.