eTOX ALLIES

eTOX ALLIES automates ligand-binding free energy prediction to estimate ligand affinities for drug discovery and toxicological assessment.

Key Features:

• Automated workflow: Performs docking, ligand topology creation, molecular dynamics simulations, and data analysis for binding free-energy estimation.
• Linear Interaction Energy (LIE): Implements the linear interaction energy method derived from Free Energy Perturbation theory for end-point free energy calculations.
• Physical interaction modeling: Accounts for steric and electrostatic interactions, solvent effects, and thermal fluctuations relevant to ligand–protein binding.
• Model creation and calibration: Provides functionalities to create and calibrate predictive models for affinity estimation.

Scientific Applications:

• Drug discovery prioritization: Ranks and prioritizes screening and synthesis of new drug candidates by estimating ligand affinities toward biological targets.
• Toxicological assessment: Predicts ligand-binding free energies to support toxicology evaluations of chemical compounds.
• Binding mechanism analysis: Assesses cases where protein flexibility, solvent effects, and binding-site interactions significantly influence ligand–protein binding strength.

Methodology:

Uses docking, ligand topology creation, molecular dynamics simulations, and data analysis together with the linear interaction energy method (derived from Free Energy Perturbation theory), modeling steric and electrostatic interactions, solvent effects, thermal fluctuations, and supporting model creation and calibration.