TIES

TIES performs relative binding free energy (RBFE) calculations using thermodynamic integration with enhanced sampling and a dual-topology approach to support ligand binding affinity prediction in drug discovery.

Key Features:

• Relative Binding Free Energy (RBFE) calculations: Computes free energy differences between ligand-bound and unbound states using thermodynamic integration with enhanced sampling.
• Dual-Topology Approach: Implements dual topologies for alchemical transformations between ligands to model binding events precisely.
• Molecular Dynamics Engine Support: Compatible with NAMD and OpenMM for performing molecular dynamics simulations.

Scientific Applications:

• Drug discovery and lead optimization: Predicts binding affinities of ligands to target proteins to prioritize and optimize candidate compounds.
• Ligand–protein binding studies: Quantifies free energy differences to assess ligand binding thermodynamics and relative potency.
• Method validation and benchmarking: Has validated performance on publicly available datasets for reliability in RBFE studies.

Methodology:

TIES uses thermodynamic integration combined with enhanced sampling, a dual-topology alchemical strategy, and molecular dynamics simulations (NAMD and OpenMM) to compute free energy differences between bound and unbound ligand states.