Truly Target-Focused Pharmacophore Modeling: A Novel Tool for Mapping Intermolecular Surfaces
AbstractPharmacophore models are an accurate and minimal tridimensional abstraction of intermolecular interactions between chemical structures, usually derived from a group of molecules or from a ligand-target complex. Only a limited amount of solutions exists to model comprehensive pharmacophores using the information of a particular target structure without knowledge of any binding ligand. In this work, an automated and customable tool for truly target-focused (T²F) pharmacophore modeling is introduced. Key molecular interaction fields of a macromolecular structure are calculated using the AutoGRID energy functions. The most relevant points are selected by a newly developed filtering cascade and clustered to pharmacophore features with a density-based algorithm. Using five different protein classes, the ability of this method to identify essential pharmacophore features was compared to structure-based pharmacophores derived from ligand-target interactions. This method represents an extremely valuable instrument for drug design in a situation of scarce ligand information available, but also in the case of underexplored therapeutic targets, as well as to investigate protein allosteric pockets and protein-protein interactions. View Full-Text
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Mortier, J.; Dhakal, P.; Volkamer, A. Truly Target-Focused Pharmacophore Modeling: A Novel Tool for Mapping Intermolecular Surfaces. Molecules 2018, 23, 1959.
Mortier J, Dhakal P, Volkamer A. Truly Target-Focused Pharmacophore Modeling: A Novel Tool for Mapping Intermolecular Surfaces. Molecules. 2018; 23(8):1959.Chicago/Turabian Style
Mortier, Jérémie; Dhakal, Pratik; Volkamer, Andrea. 2018. "Truly Target-Focused Pharmacophore Modeling: A Novel Tool for Mapping Intermolecular Surfaces." Molecules 23, no. 8: 1959.
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