NEMAT

NEMAT performs automated nonequilibrium alchemical transformations to predict ligand binding affinities in membrane protein systems.

Key Features:

• Automated Nonequilibrium Alchemical Transformations: NEMAT automates nonequilibrium free-energy calculations for ligand binding in water, membranes, and membrane-embedded protein environments.
• Membrane Protein Specialization: NEMAT is tailored for membrane protein systems where setup and analysis are complex and error-prone.
• Free-Energy Decomposition: NEMAT decomposes binding free energy into membrane-partitioning and protein-specific components for mechanistically interpretable predictions.
• Systematic Parameter Control: NEMAT provides systematic control over critical simulation parameters to optimize free-energy estimates.
• Reproducibility and Automation: NEMAT reduces manual intervention and improves consistency across simulations through a structured, modular workflow.

Scientific Applications:

• Ligand Binding Affinity Prediction: NEMAT predicts binding affinities of small-molecule ligands to membrane proteins with accuracy comparable to established equilibrium methods.
• Membrane-Partitioning Analysis: NEMAT dissects membrane and protein contributions to binding free energy for membrane-embedded targets.
• Drug Discovery for Membrane Proteins: NEMAT supports computational prediction of binding energies for P2Y1 ligands and other membrane protein targets.

Methodology:

NEMAT uses nonequilibrium molecular dynamics simulations to perform alchemical transformations, estimating ligand binding affinities through non-equilibrium free-energy calculations in water, membrane, and membrane-embedded protein environments.