Binding Free Energy Redefined: Accurate, Fast, and Cost Effective
Chris Neale, Gaetano Calabró, Agnes Huang, and Lukas Eberlein
OpenEye, Cadence Molecular Sciences, 9 Bisbee Court Suite D, Santa Fe, NM 87508
Summary:
Product Keywords: Orion®, MD, Free Energy Nonequilibrium Switching, FE-NES
Abstract:
Computational estimation of ligand-protein binding free energies is essential in the lead optimization phase of drug discovery. Industry scientists have reported that OpenEye’s Free Energy Nonequilibrium Switching (FE-NES) offers a 5-10X higher throughput and 2-5X more cost-effective alternative to traditional methods like free energy perturbation or thermodynamic integration, which typically require extensive sampling near equilibrium.
Our FE-NES implementation on the Orion® molecular design cloud platform provides automated calculations, even for large ligand sets, in just a few hours.
FE-NES delivers accuracy on par with industry-leading solutions, making it an ideal tool for daily lead optimization tasks.
OpenEye’s FE-NES delivers market-leading accuracy, while being 5–10X higher throughput and 2–5X more cost-effective than other methods. Data sets originally curated in [1, 2].
Users can adjust FE-NES parameters to balance accuracy and throughput, enabling cost-effective ranking of hundreds or thousands of molecules in precise results for lead optimization. With various map types (including efficient star maps and networked OELOMAPs with cycle closure) and an interactive interface, users can leverage their expertise while keeping costs low and accuracy high, ensuring maximum value .
[1] Wang et al., 2015, J. Am. Chem. Soc., 137: 2695.
[2] Schindler et al., 2020, J. Chem. Inf. Model., 60: 5457
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