Permeability (electromagnetism)

Biological system

Membrane

Biology

Chemistry

In vitro

Data science

Lipid bilayer

Computer science

Drug discovery

Membrane permeability

Model validation

Simulation

Biochemistry

Computational model

The Journal of Physical Chemistry B

Membrane permeability is a key property to consider during the drug design process, and particularly vital when dealing with small molecules that have intracellular targets as their efficacy highly depends on their ability to cross the membrane. In this work, we describe the use of umbrella sampling molecular dynamics (MD) computational modeling to comprehensively assess the passive permeability profile of a range of compounds through a lipid bilayer. The model was initially calibrated through in vitro validation studies employing a parallel artificial membrane permeability assay (PAMPA). The model was subsequently evaluated for its quantitative prediction of permeability profiles for a series of custom synthesized and closely related compounds. The results exhibited substantially improved agreement with the PAMPA data, relative to alternative existing methods. Our work introduces a computational model that underwent progressive molding and fine-tuning as a result of its synergistic collaboration with numerous in vitro PAMPA permeability assays. The presented computational model introduces itself as a useful, predictive tool for permeability prediction.

Predicting a Drug’s Membrane Permeability: A Computational Model Validated With <i>in Vitro</i> Permeability Assay Data

Predicting a Drug’s Membrane Permeability: A Computational Model Validated With in Vitro Permeability Assay Data