Calculating Absolute Binding Free Energies of Tyk2 Inhibitors

Zeke A. Piskulich¹, Patricio Barletta¹, and Darrin M. York¹

¹Laboratory for Biomolecular Simulation Research, Institute for Quantitative Biomedicine and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA

Learning objectives

• Use FFPOPT to Run Dihedral Scans for a Simple Molecule

• Use FFPOPT with a Machine Learning Potential to Fit New Dihedral Parameters

Relevant literature

• Coming Soon!

Tutorial

Running ABFE Calculations with AmberFlow

In this section, we will walk through how to use AmberFlow to set up and run absolute binding free energy calculations (ABFE) for a Tyk2 inhibitor.

The files you will need are located here:

• Download the tutorial files

If you have not already done so, please follow the instructions in the amberflow documentation to install amberflow and set up your environment.

Warning

Currently AmberFlow Documentation is not available online - this should be updated when that changes.

Now, we will walk through the steps to get set up to run ABFE calculations with AmberFlow.

The first step is to unpack the tutorial files; here we will unpack them into a directory called abfe_tyk2_tutorial:

mkdir abfe_tyk2_tutorial
cd abfe_tyk2_tutorial
tar -xvzf ../tutorial_files.tar.gz

In this folder, you will have the following files: