Journal of Medicinal Chemistry · 2006 · 113 citations · 42 references
Natural SciencesBiophysicsMolecular BiologyMolecular BiophysicsStructural BiologyStructural BiophysicsHydration EffectsLigand BindingMolecular DockingProtein-ligand DockingRna BiophysicsRna StructureConformational EnsemblesHydration Shell EnergeticsHydration Shell StructureLigand-protein DockingProtein-nucleic Acid DockingRna HydrationRoot-mean-square DeviationSolvent Effects In Docking
Although much effort has been devoted to the development of programs suited for the docking of ligands to proteins, much less progress has been achieved in the nucleic acid field. We have developed a unique approach for docking aminoglycosides to RNA considering the flexibility of these macromolecules using conformational ensembles and accounting for the role of the first hydration shell. This concept, successfully implemented in AutoDock, relies on the computation of the intermolecular interaction energy that accounts for the presence of dynamically bound water molecules to the RNA. As an application, a set of 11 aminoglycosides was docked with an average root-mean-square deviation (RMSD) of 1.41 A to be compared with an average RMSD of 3.25 A when the original AutoDock protocol was used.
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