Absolute alchemical binding free energy calculation for the SARS-CoV-2 main viral protease (Mpro)
This video from the Voelz lab shows an absolute alchemical binding free energy calculation for a compound binding to the SARS-CoV-2 main viral protease (Mpro).
About the calculations
We are using a method called free energy perturbation, or FEP, to estimate the affinity of a potential drug molecule to its receptor. FEP methods are very expensive compared to other methods like docking, but with the advantages of high accuracy and physical insight. We are using protocols very similar to those used in the most recent SAMPL blind challenge.
The calculation involves decoupling the drug molecule (by turning off its electrostatic and dispersion interactions) from its receptor, and again for a molecule in water. For the latter type of simulations, unfortunately there’s not much to look at the Folding@home viewer, because there’s no protein being simulated. However boring these projects appear, please keep in mind that they are absolutely essential to our success.