On-the-Fly QM/MM Docking with Attracting Cavities.

Détails

ID Serval
serval:BIB_47CBD7F371A0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
On-the-Fly QM/MM Docking with Attracting Cavities.
Périodique
Journal of Chemical Information and Modeling
Auteur(s)
Chaskar P., Zoete V., Röhrig U.F.
ISSN
1549-960X (Electronic)
ISSN-L
1549-9596
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
57
Numéro
1
Pages
73-84
Langue
anglais
Résumé
We developed a hybrid quantum mechanical/molecular mechanical (QM/MM) on-the-fly docking algorithm to address the challenges of treating polarization and selected metal interactions in docking. The algorithm is based on our classical docking algorithm Attracting Cavities and relies on the semiempirical self-consistent charge density functional tight-binding (SCC-DFTB) method and the CHARMM force field. We benchmarked the performance of this approach on three very diverse data sets: (1) the Astex Diverse set of 85 common noncovalent drug/target complexes formed both by hydrophobic and electrostatic interactions; (2) a zinc metalloprotein data set of 281 complexes, where polarization is strong and ligand/protein interactions are dominated by electrostatic interactions; and (3) a heme protein data set of 72 complexes, where ligand/protein interactions are dominated by covalent ligand/iron binding. Redocking performance of the on-the-fly QM/MM docking algorithm was compared to the performance of classical Attracting Cavities, AutoDock, AutoDock Vina, and GOLD. The results demonstrate that the QM/MM code preserves the high accuracy of most classical scores on the Astex Diverse set, while it yields significant improvements on both sets of metalloproteins at moderate computational cost.

Mots-clé
Ligands, Molecular Docking Simulation, Protein Binding, Protein Conformation, Proteins/chemistry, Proteins/metabolism, Quantum Theory
Pubmed
Web of science
Création de la notice
06/12/2017 16:17
Dernière modification de la notice
03/03/2018 16:50
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