Exploring different virtual screening strategies for acetylcholinesterase inhibitors.

The virtual screening problems associated with acetylcholinesterase (AChE) inhibitors were explored using multiple shape, and structure-based modeling strategies. The employed strategies include molecular docking, similarity search, and pharmacophore modeling. A subset from directory of useful decoy...

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Publicado en:BioMed Research International Vol. 2013; pp. 236850 - 236851
Autores principales: Mishra, Nibha, Basu, Arijit
Formato: Journal Article
Publicado: Wiley-Blackwell 2013
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2013
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: Exploring different virtual screening strategies for acetylcholinesterase inhibitors.
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        au:
          Mishra, Nibha
          Basu, Arijit
        affil: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, India.
      sug:
        subj:
          Acetylcholinesterase Metabolism
          Cholinesterase Inhibitors Analysis
          Cholinesterase Inhibitors Pharmacodynamics
          Drug Evaluation, Preclinical
          User-Computer Interface
          Cholinesterases Metabolism
          Amino Acids
          Laboratory Chemicals
          Models, Theoretical
          Proteins
          ROC Curve
      ab: The virtual screening problems associated with acetylcholinesterase (AChE) inhibitors were explored using multiple shape, and structure-based modeling strategies. The employed strategies include molecular docking, similarity search, and pharmacophore modeling. A subset from directory of useful decoys (DUD) related to AChE inhibitors was considered, which consists of 105 known inhibitors and 3732 decoys. Statistical quality of the models was evaluated by enrichment factor (EF) metrics and receiver operating curve (ROC) analysis. The results revealed that electrostatic similarity search protocol using EON (ET.combo) outperformed all other protocols with outstanding enrichment of >95% in top 1% and 2% of the dataset with an AUC of 0.958. Satisfactory performance was also observed for shape-based similarity search protocol using ROCS and PHASE. In contrast, the molecular docking protocol performed poorly with enrichment factors <30% in all cases. The shape- and electrostatic-based similarity search protocol emerged as a plausible solution for virtual screening of AChE inhibitors.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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