In this slide I presented the Computer Aided Drug Design and its type : 1.Structure based Drug Design 2. Ligand based Drug Design and its Applications.

1. Rani T. Bhagat
M . Pharmacy,
(Pharmaceutical Chemistry)
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2. CONTENT
 HISTORY
 INTRODUCTION
DRUG DESIGN-CADD
TYPES
TECHNIQUES
APPLICATION
REFERANCES
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3. HISTORY
• Early 19th century –extraction of compounds from plants
(morphine , cocain).
• Late 19th century – fewer natural products used ,more synthetic
substances. Dye and chemical companies start research labs and
discover medical application .(Bayer)
• 1905 –John Langley :Theory of receptive substances which
started “The concept of specific receptors that bind drug or
transmitter substances onto the cell, either initiating biological
effects or inhibiting cellular function”
• 1909 – First Rational drug design.
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4. • 1960- First successful attept to relate chemical structure to
biological action quantitatively.
• Mid to late 20th century –understand disease states ,
biological structure ,processes, drug transport, distribution,
metabolism.
• Medicinal chemist this knowledge to modify chemical
structure to influence a drug’s activity ,stability.
• The time from conception to approval of a new drug is
typically 10-15 years.
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5. DRUG DESIGN
• The primary object of medicinal chemistry is the design and
discovery of new compound that are suitable for use as drug.
• It is inventive process of finding new medication based on the
knowledge of biological target called as drug design.
• Drug design with the help of computer may be used at any of the
following stages of drug discovery.
– Hit identification using vertual screening
– QSAR
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6. CADD
• Computer Aided Drug Design is the computer based technique
used in the computational chemistry to discover , enhances or
study of drugs and related biologically active molecules.
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8. Structure based drug design (direct)
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9. DENOVO DRUG DESIGN
• It is a process in which the 3D – structure of receptor is used to
design newer molecules .
• It involve structural determination of the lead target complexes and
lead modification using molecular modelling.
• The “De novo ligand design” “De novo inhibitor design” and “De
novo drug design” are sometimes used as interchangebly.
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10. PHARMACOPHORE MODELLING
• “The schematic representation of nature of bioactive functional groups along with there
interatomic distance is known as pharmacophore”
• A pharmacophore represents molecules features including as
 3D (Hydrophobic group, charged or ionizable group, hydrogen donar or accepter)
 2D (Substructural)
 1D (Physical or Biological Properties)
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11. Ligand based drug design (indirect)
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12. QSAR
• QSAR are mathematical relationship between chemical structure
and pharmacological activity in a quantitative manner for series of
compounds.
• PARAMETERS-1)Hydrophobic parameter
2)Steric parameter
3)Electronic parameter
• METHODS- 1) Hansch Analysis
2) Free- Wilson Analysis
3) Mixed Approach
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13. LIGAND BASED VIRTUAL SCREENING
• A Candidate ligand can then be compared to the pharmacophore model to
compared to the Pharmacophore model to determine whether it is compatible
with it and likely to kind.
• Another approach to ligand – based virtual screening is to use 2D chemical
similarity analysis methods to
scan a database of molecules
against one or more active
ligand structure.
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14. application
 Determine the lowest free energy structure for the receptor –
ligand complex .
 Search database and rank hits for lead generation.
 Calculate the differential binding of a ligand to two different
macromolecules receptors.
 Study the geometry of particular complex.
 Propose modification of a lead molecules to optimize potency
or other properties.
 De novo design for lead generation.
 Used foe docking study
 Used for SBDD and LBDD.
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