PerMM (Permeability of Molecules across Membranes) is a physics-based computational approach for predicting passive membrane permeability. It integrates heterogeneous solubility\u2013diffusion theory with the anisotropic solvent model of lipid bilayers. Using all-atom 3D solute structures, PerMM calculates transbilayer free energy profiles, optimal orientations, and translocation pathways by moving conformers across implicit DOPC bilayers. From these energy landscapes, permeability coefficients are obtained by integrating local resistances, assuming size-dependent diffusivity.<\/p>
The method accounts for hydrophobic, electrostatic, and hydrogen-bonding interactions, as well as ionization equilibria within the anisotropic bilayer environment. Validation against experimental datasets (BLM, PAMPA, BBB, Caco-2\/MDCK) demonstrated strong predictive accuracy. Unlike empirical QSPR models, PerMM is not trained on specific data but relies on physical principles, making it broadly applicable across diverse chemical scaffolds.<\/p>
<\/p>","categories":[{"id":9,"title":"Mechanistic","breadcrumb":[{"id":5,"title":"Computed"},{"id":9,"title":"Mechanistic"}]}],"url":"https:\/\/molmedb.upol.cz\/api\/v1\/methods\/27","landing_page":"https:\/\/molmedb.upol.cz\/method\/27","created_at":"2018-06-30T19:09:31.000000Z","updated_at":"2026-06-29T12:43:05.000000Z"}}