Department of Pharmaceutical Sciences, University of Milan
The lecture will present the recently developed Nwat-MMGBSA (or Nwat-MMPBSA, depending on the chosen solvation model) method, derived from the popular MM-(PB)GBSA.
The method allow the inclusion of a given number of explicit water molecules, that are the closest to the ligand in each frame of a molecular dynamics (MD) trajectory, in the MM-(PB)GBSA calculations.
By using this “hybrid” implicit-explicit solvation, with a fixed number of waters among all the considered frames, the correlation between calculated and experimental binding energies in ligand-receptor and protein-protein complexes can be increased, compared to the default implicit solvent calculations.
The protocol for MD simulations, preparatory to Nwat-MMGBSA calculations, has been optimized to maximize efficacy and efficiency, thus making the calculations practical in low-to-medium throughput virtual screenings.
Rescoring of docking results can be performed on a regular workstation equipped by a GPU card, taking one-two hour per ligand for the complete process (from parameterization to binding energy calculation), averagely.
In the tutorial session, we will see how to use a set of scripts to automatize a complete structure based virtual screening workflow, going from library setup to docking and rescoring.
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