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An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

preprint
submitted on 08.09.2017 and posted on 11.09.2017 by Irene Maffucci, Xiao Hu, Valentina Fumagalli, Alessandro Contini
The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The method was shown to improve the correlation between predicted and experimental binding energy in both ligand-receptor and protein-protein complexes (Maffucci & Contini, JCIM 2016, 56, 1692). Here, we report on the optimization of the Nwat-MMGBSA protocol for its use to rescore docking results. We also report an automatic workflow, based on three independent scripts (which can be concatenated in a fully automated procedure) to easily employ Nwat-MMGBSA rescoring in virtual screening application. The protocol has been tuned using three different examples, and then tested in two retrospective virtual screening examples. In each example, the Nwat-MMGBSA method has been compared with the standard MMGBSA approach (Nwat=0). A link to download the scripts, working examples and tutorials is also provided.

Funding

MIUR through the “FIRB—Programma ‘Futuro in Ricerca’” (grant No. RBFR087YAY); Horizon 2020 under the Marie Skłodowska-Curie ITN-European Joint Doctorate, grant agreement No. 675527, MOGLYNET; NVIDIA through the GPU Grant Program

History

Topic

  • Computational chemistry and modeling

Email Address of Submitting Author

alessandro.contini@unimi.it

Institution

Università degli Studi di Milano

Country

Italy

ORCID For Submitting Author

0000-0002-4394-8956

Declaration of Conflict of Interest

no conflict of interest

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