pharmacophore mapping

pharmacophore mapping

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  PHARMACOPHORE MAPPING AND PHARMACOPHORESCREENING PRESENTED BY ASHUTOSH B. MAHALE M .PHARMACY IST YEAR ( PHARMACOLOGY ) UNIVERSITY DEPARTMENT OF PHARMACEUTICAL SCIENCES, R.T.M NAGPUR UNIVERSITY , NAGPUR
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   First introducedin 1990 by “Paul Herilich”.  Refer as “A molecular framework that is recognized as a receptor site with essential features responsible for a drug’s biological activity”. PHARMACOPHORE That substructure of a molecule that is responsible for its pharmacological activity (c.f. chromophore) A set of geometrical constraints between specific functional groups that enable the molecule to have biological activity
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   A pharmacophorerepresents molecules features including as  3D (Hydrophobic group, charged/ ionizabel group ,H donor or acceptor )  2D (Substructures)  1D (Physical or biological properties
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  Overview of Pharmacophore-basedDrug Design Generate pharmacophoreActivity data Test activity Search compound library for actives Buy or synthesise ‘hits’ pharmacophore.org 7
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  Method There aretwo broad categories of screening techniques: ligand based and structure based (i)Ligand based - Given a set of structurally diverse ligands that binds to a receptor These are known as Pharmacophore models. A candidate ligand can then be compared to the Pharmacophore model to d d etermine whether it is compatible with it and therefore likely to bind (ii) Structure based- Structure based virtual screening involves docking of candidate ligands into a protein target followed by applying a scoring function to estimate the likelihood that the ligand will bind to the protein with high affinity
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  Pharmacophore Mapping anddesigning •Where QSAR focused on a set of descriptors like electrostatic and thermodynamic properties, Pharmacophore Mapping is a geometrical approach • A pharmacophore can be thought of as a 3D model of characteristic features of the binding site of the investigated protein • Like QSAR models, pharmacophores can be built without knowing the structure of the target • This can be done by extracting features from compounds which are known to interact with the target then the derived pharmacophore model can be used to identify compound databases (libraries) thus screening for potential drug candidates that may be of interest
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  Pharmacophore Mapping Software Discovery Studio  Ligand Scout
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  Conclusion • The pharmacophoreconcept is a successful and well-known approach for drug design (both ligand and structure based) •Pharmacophore mapping is a promising concept in the development of drug within shorter time and limited resources when compared with the conventional drug development process 30
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