Discovery of Novel Acetylcholinesterase Inhibitors by Virtual Screening, In Vitro Screening, and Molecular Dynamics Simulations
C. Johan van der Westhuizen, André Stander, Darren L. Riley, Jenny‐Lee Panayides
Abstract
]pyridin-6-amine both of which are noted to be promising compounds for further optimization. As various possible binding poses were suggested from molecular docking, molecular dynamics simulations were employed to validate the poses. In the case of the most active compounds identified, a critical, stable water bridge formed deep within the binding pocket was identified potentially explaining in part the lack of activity for subsets of compounds that are not able to form this water bridge.
Topics & Concepts
Virtual screeningAcetylcholinesteraseDrug discoveryComputational biologyHigh-throughput screeningDocking (animal)ChemistryMolecular descriptorMolecular dynamicsCombinatorial chemistryQuantitative structure–activity relationshipStereochemistryBiochemistryEnzymeBiologyComputational chemistryMedicineNursingComputational Drug Discovery MethodsCholinesterase and Neurodegenerative DiseasesEnzyme function and inhibition