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Congrats to Si on new JCTC paper

Congrats to graduate student Si Zhang on the publication of her first-author manuscript in JCTC!

This work was a collaboration with David Hahn (Janssen Research) of Open Force Field fame, and Michael R. Shirts (University of Colorado-Boulder) who originated and implemented this expanded ensemble (EE) method in GROMACS.

We were turned on to the EE approach during our work with the COVID Moonshot, where we used CPU clients on
Folding@home to screen 50k+ potential SARS-CoV-2 main protease (Mpro) inhibitors by their estimated absolute binding free energy (ABFE).

Si realized that no one had yet applied this approach to calculating relative free energies. So she tested it for a set of 24 transformations between 16 Tyk2 inhibitors using the OpenFF “Parsely” small-molecule force field, and it worked very well, achieving an accuracy within 0.66 kcal/mol (MUE) of the experimental value! Another result that portends well for using EE on distributed computing platforms like Folding@home: Performing N independent simulations gives better accuracy than a single simulation N times as long.

You can read all about the details in our hot-off-the-press paper:

Zhang, Si, David F. Hahn, Michael R. Shirts, and Vincent A. Voelz. “Expanded Ensemble Methods Can Be Used to Accurately Predict Protein-Ligand Relative Binding Free Energies.” Journal of Chemical Theory and Computation 17, no. 10 (October 12, 2021): 6536–47.

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