An exponential logarithmic measure of drug receptor binding and saturation

TL;DR

The paper introduces an exponential logarithmic descriptor (ELD) that combines thermodynamic and probabilistic models to better characterize ligand-receptor binding and saturation across various concentration regimes.

Contribution

It presents a novel ELD measure integrating thermodynamic and exponential relations, offering improved dynamic range and sensitivity over traditional occupancy curves.

Findings

ELD retains broader dynamic range than conventional measures.

ELD reveals asymmetric sensitivity at low and high concentrations.

Numerical simulations demonstrate ELD's effectiveness across different affinity and exposure conditions.

Abstract

Ligand receptor interactions are commonly assessed through equilibrium occupancy and pharmacodynamic measures that describe binding and saturation by means of bounded response curves. Thermodynamic approaches relate binding affinity to logarithmic concentration scaling, while probabilistic descriptions of occupancy arise from exponential relations. We introduce an exponential logarithmic descriptor (ELD) that integrates ligand availability and thermodynamic binding propensity within a single quantity. The logarithmic component corresponds to a thermodynamic term derived from concentration dependent free energy relations, whereas the exponential component is represented through an inverse normalized concentration term corresponding to the reciprocal of the exponential occupancy factor emerging from Boltzmann type binding formulations. We explored ELD behavior through numerical simulations spanning sub affinity, transition and saturating concentration regimes under multiple affinity conditions and time dependent exposure profiles. Compared with conventional occupancy curves, ELD retained a broader dynamic range and revealed asymmetric sensitivity across concentration scales, particularly at low exposure and near saturation, where bounded occupancy measures progressively compress variability. The resulting behavior reflects the coexistence of amplification and constraint processes within ligand receptor dynamics. ELD may provide quantitative representation for biological systems in which exponential and logarithmic processes coexist across different scales. Potential applications include characterization of dose response transitions, identification of subtherapeutic and saturating exposure states, comparison of compounds with different affinities, normalization across heterogeneous datasets and continuous tracking of pharmacodynamic regimes during time dependent exposure.