Data from: Antibiotic uptake across gram-negative outer membranes: better predictions towards better antibiotics

Crossing the gram-negative bacterial membrane poses a major barrier to antibiotic development, as many small molecules that can biochemically inhibit key bacterial processes are rendered microbiologically ineffective by their poor cellular uptake. The outer membrane is the major permeability barrier for many drug-like molecules, and the chemical properties that enable efficient uptake into mammalian cells fail to predict bacterial uptake. We have developed a computational method for accurate prospective prediction of outer-membrane uptake of drug-like molecules, which we combine with a new medium-throughput experimental assay of outer membrane vesicle swelling. Parallel molecular dynamics simulations of compound uptake through E. coli OmpF are used to successfully and quantitatively predict experimental permeabilities measured via either outer membrane swelling or via prior liposome swelling measurements. These simulations are analyzed using an inhomogeneous solubility-diffusion model to yield predictions of permeability. For most polar molecules we test, outer membrane permeability also correlates well with whole-cell uptake. The ability to accurately predict and measure outer-membrane uptake of a wide variety of small molecules will enable simpler determination of which molecular scaffolds and which derivatives are most promising prior to extensive chemical synthesis. It will also assist in formulating a more systematic understanding of the chemical determinants of outer-membrane permeability.Files include Gromacs compiled run input files (TPR), run parameter files, and small molecule parameters for each small molecule tested prospectively in the accompanying publication. Funding provided by: Knut and Alice Wallenberg FoundationCrossref Funder Registry ID: Award Number: Funding provided by: Wallace Coulter FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100001062Award Number:Simulation parameters and starting files for simulations of small-molecule permeability through OmpF porins in bacterial outer membranes