Rescoring docking results

Rescoring docking results by Molecular Dynamics and Nwat-MMGBSA calculations
Rescoring docking results by Molecular Dynamics and Nwat-MMGBSA calculations

Alessandro Contini
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.[1]

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,[2] 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.[3]

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.

1. I. Maffucci and A. Contini J. Chem. Theor. Comput. 9, 2706 (2013)
2. I. Maffucci and A. Contini J. Chem. Inf. Model. 56, 1692 (2016).
3. I. Maffucci, X. Hu, V. Fumagalli, A. Contini Front. Chem., 05 March 2018 |