Effect of set up protocols on the accuracy of alchemical free energy calculation over a set of ACK1 inhibitors
J. M. Granadino-Roldán, A. S. J. S. Mey, J. J. Pérez González, S. Bosisio, J. Rubio- Martinez, J. Michel.
PLoS ONE 14 (2019) e0213217.
Snapshot taken after 2 ns of MD showing the manually placed water molecule inside the ATP-binding pocket.
Hit-to-lead virtual screening frequently relies on a cascade of computational methods that starts with rapid calculations applied to a large number of compounds and ends with more expensive computations restricted to a subset of compounds that passed initial filters. This work focuses on set up protocols for alchemical free energy (AFE) scoring in the context of a Docking – MM/PBSA – AFE cascade.