Physics-Based Method for Modeling Passive Membrane Permeability and Translocation Pathways of Bioactive Molecules.

ABSTRACT: Assessment of permeability is a critical step in the drug development process for selection of drug candidates with favorable ADME properties. We have developed a novel physics-based method for fast computational modeling of passive permeation of diverse classes of molecules across lipid membranes. The method is based on heterogeneous solubility-diffusion theory and operates with all-atom 3D structures of solutes and the anisotropic solvent model of the lipid bilayer characterized by transbilayer profiles of dielectric and hydrogen bonding capacity parameters. The optimal translocation pathway of a solute is determined by moving an ensemble of representative conformations of the molecule through the dioleoyl-phosphatidylcholine (DOPC) bilayer and optimizing their rotational orientations in

SUBMITTER: Lomize AL 

PROVIDER: S-EPMC6756154 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature