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Počítačový návrh léků: Kvantově-mechanická studia komplexů mezi proteiny a ligandy a proteiny, ligandy a vodou

  1. Title statementPočítačový návrh léků: Kvantově-mechanická studia komplexů mezi proteiny a ligandy a proteiny, ligandy a vodou [rukopis] / HARESH Babubhai ajani
    Additional Variant TitlesIn Silico Drug Design
    Personal name Babubhai ajani, HARESH, (dissertant)
    Translated titleIn Silico Drug Design
    Issue data2018
    NoteVed. práce Pavel Hobza
    Another responsib. Hobza, Pavel, 1946- (školitel)
    Another responsib. Univerzita Palackého. Katedra fyzikální chemie (degree grantor)
    Keywords Computer-Aided Drug Design * Structure-Based Drug Design * Molecular Docking * Scoring functions * Water Thermodynamics
    Form, Genre disertace dissertations
    UDC (043.3)
    CountryČesko
    Languageangličtina
    Document kindPUBLIKAČNÍ ČINNOST
    TitlePh.D.
    Degree programDoktorský
    Degree programChemie
    Degreee disciplineFyzikální chemie
    book

    book

    Kvalifikační práceDownloadedSizedatum zpřístupnění
    00219627-196347198.pdf92.2 MB02.05.2018
    PosudekTyp posudku
    00219627-ved-222755375.pdfPosudek vedoucího
    00219627-opon-389721364.pdfPosudek oponenta
    Průběh obhajobydatum zadánídatum odevzdánídatum obhajobypřidělená hodnocenítyp hodnocení
    00219627-prubeh-872177667.pdf07.11.201402.05.201819.06.2018S2

    Over the last few decades, computer-aided drug design has emerged as a most successful technique rendering the drug discovery process more efficient and less costly. In the structure-based drug design branch, three-dimensional information on the biomolecular targets is used by the docking and scoring methodologies to find and optimize new ligands. In this dissertation, the following approaches are presented: ligand design, binding mode prediction, structure-activity relationship (SAR), molecular docking, receptor-ligand scoring and bridging water thermodynamics, followed by their application in protein-ligand complexes and host-guest systems. Molecular docking, which has become a powerful and influential tool for studying molecular recognition, aims to predict the binding mode of small molecules toward their biological target. It has been used in several projects: we have predicted the binding modes of a novel and potent inhibitor of CDK2 and FLT3 kinases and covalent inhibitors of AChE, BChE. Further, semi-empirical quantum mechanics-based scoring functions (SQM/COSMO) were used in native pose recognition where the poses had been generated with several docking programs. The SQM/COSMO scoring was compared with classical scoring function. We observed that SQM/COSMO accurately predicted the native poses in two dozen of difficult and diverse protein-ligand systems. Lastly, we discuss the important role of explicit water molecules in protein kinases, hydrolases, serine racemase and host-guest systems. We determined their thermodynamical parameter G which correlated very well with the experimental binding G for protein-ligand complex and host-guest systems.

Number of the records: 1  

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