Correlation between the structure and permeability of compounds into cells or across cell layers.

The system of empirical structure-permeation analysis in the discovery of Gram-negative bacteria is characterized by two membranes with distinct permeability properties, active drug efflux, and bacterial species-specific differences in the composition and properties of the membranes and efflux pumps. These complexities severely complicate structure–permeation and structure-activity relationships.

Despite recent advances in understanding the Gram-negative permeability barrier, the problem of predicting small-molecule permeability in Gram-negative bacteria remains largely unsolved.