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Drug efficacy depends on its capacity to permeate across the cell membrane. We consider the prediction of passive drug-membrane permeability coefficients. Beyond the widely recognized correlation with hydrophobicity, we additionally consider the functional relationship between passive permeation and acidity. To discover easily interpretable equations that explain the data well, we use the recently proposed sure-independence screening and sparsifying operator (SISSO), an artificial-intelligence technique that combines symbolic regression with compressed sensing. Our study is based on a large in silico dataset of 0.4 million small molecules extracted from coarse-grained simulations. We rationalize the equation suggested by SISSO via an analysis of the inhomogeneous solubility-diffusion model in several asymptotic acidity regimes. We further extend our analysis to the dependence on lipid-membrane composition. Lipid-tail unsaturation plays a key role, but surprisingly contributes stepwise rather than proportionally. Our results are in line with previously observed changes in permeability, suggesting the distinction between liquid-disordered (Ld) and liquid-ordered (Lo) permeation. Together, compressed sensing with analytically derived asymptotes establish and validate an accurate, broadly applicable, and interpretable equation for passive permeability across both drug and lipid-tail chemistry.
To shorten the time required to find effective new drugs, like antivirals, a key parameter to consider is membrane permeability, as a compound intended for an intracellular target with poor permeability will have low efficacy. Here, we present a comp
Motivated by the mechanics of dynamin-mediated membrane tube fission we analyse the stability of fluid membrane tubes subjected to shear flow in azimuthal direction. We find a novel helical instability driven by the membrane shear flow which results
An analytical model of mechanical stress in a polymer electrolyte membrane (PEM) of a hydrogen/air fuel cell with porous Water Transfer Plates (WTP) is developed in this work. The model considers a mechanical stress in the membrane is a result of the
Under typical PEM fuel cell operating conditions, part of membrane electrode assembly is subjected to humidity cycling due to variation of inlet gas RH and/or flow rate. Cyclic membrane hydration/dehydration would cause cyclic swelling/shrinking of t
Although many equations of state of hard-disk fluids have been proposed, none is capable of reproducing the currently calculated or estimated values of the first eighteen virial coefficients at the same time as giving very good accuracy when compared