USW
Computational ChemistryFree EnergyHardSeed

Free-energy perturbation for relative binding affinity

Run alchemical FEP to rank congeneric ligands and match experimental ΔΔG.

Dr. Yuki Sato
Molecular Simulation Lab
Accurate relative binding free energies at scale
Nature Communications · 2023
~2 days (GPU)
registered 2025-08-27
FEPMDbinding

End goal

Predict ΔΔG with RMSE ≤ 1.0 kcal/mol across the series.

Overview

The agent sets up an alchemical perturbation network across a congeneric series, runs the MD legs, and reports relative binding free energies benchmarked to experiment.

Tools allowed

1
GROMACS·HPC

Workflow

1-step protocol

Each step is verified against the scientist's targets. Open any simulation to test it live.

  1. 1

    Perturb & analyze

    Step 1 / 1

    Run the perturbation network and estimate ΔΔG.

    Protocol

    1. aBuild the perturbation map.
    2. bRun MD legs.
    3. cEstimate ΔΔG with cycle closure.

    Targets

    ΔΔG RMSE≤1kcal/mol
    Cycle closure≤0.5kcal/mol
    Expected output

    Relative binding free energies for the series.

    Simulations · click to test