Search results for "LigandScout"

showing 3 items of 3 documents

Common Hits Approach: Combining Pharmacophore Modeling and Molecular Dynamics Simulations.

2017

We present a new approach that incorporates flexibility based on extensive MD simulations of protein-ligand complexes into structure-based pharmacophore modeling and virtual screening. The approach uses the multiple coordinate sets saved during the MD simulations and generates for each frame a pharmacophore model. Pharmacophore models with the same pharmacophore features are pooled. In this way the high number of pharmacophore models that results from the MD simulation is reduced to only a few hundred representative pharmacophore models. Virtual screening runs are performed with every representative pharmacophore model; the screening results are combined and rescored to generate a single hi…

0301 basic medicineGeneral Chemical EngineeringDrug Evaluation PreclinicalLibrary and Information SciencesMolecular Dynamics Simulationcomputer.software_genreLigandsLigandScoutCommon Hits Approach (CHA)03 medical and health sciencesMolecular dynamicsUser-Computer InterfaceComputational chemistryPharmacophore ModelingFlexibility (engineering)Virtual screeningChemistryFrame (networking)ProteinsGeneral ChemistryInto-structureSettore CHIM/08 - Chimica FarmaceuticaComputer Science Applications030104 developmental biologyData miningPharmacophorecomputerJournal of chemical information and modeling
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Evaluating the stability of pharmacophore features using molecular dynamics simulations.

2016

Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …

0301 basic medicineProtein FlexibilityProtein ConformationBiophysicsStability (learning theory)Molecular Dynamics SimulationLigands01 natural sciencesBiochemistryLigandScoutSet (abstract data type)03 medical and health sciencesMolecular dynamicsComputational chemistryFeature (machine learning)Pharmacophore ModelingSensitivity (control systems)Molecular BiologyBinding Sites010405 organic chemistryChemistryStructure-based Pharmacophore ModelingMolecular DynamicProteinsHydrogen BondingCell Biology0104 chemical sciences030104 developmental biologyRankingModels ChemicalDrug DesignPharmacophoreBiological systemProtein BindingBiochemical and biophysical research communications
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Comparing molecular dynamics-derived pharmacophore models with docking: A study on CDK-2 inhibitors

2020

Abstract We compared the performance of molecular dynamics (MD)-derived pharmacophore modeling approaches, Common Hit Approach (CHA), and the Molecular dYnamics SHAred PharmacophorE (MYSHAPE) approach, with semi-flexible constrained/unconstrained docking. The aim of this work is to enrich the hit-list of a virtual screening on CDK-2 known inhibitors as a case study. Cyclin-dependent kinases (CDKs) deregulation is associated with cancer growth. CDKs are an attractive target for anticancer agents. MD-derived pharmacophore models have been obtained with LigandScout 4.2.1. Docking analysis has been performed through Glide 7.6. The results highlighted the MYSHAPE approach has a better performanc…

CDK2Virtual screeningbiologyPharmacophore010405 organic chemistryChemistryGeneral ChemistryComputational biologyMolecular dynamics010402 general chemistry01 natural sciencesDynamic pharmacophoreLigandScout0104 chemical sciencesDockingMolecular dynamicsCyclin-dependent kinaseDocking (molecular)biology.proteinPharmacophore
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