Pharmacophore modeling and docking techniques are important in rational drug design. Pharmacophore modeling identifies common molecular features necessary for biological activity. It represents features as 3D structures, 2D substituents, or properties. Pharmacophore modeling is used in structure-based drug design through target identification and ligand-based design via virtual screening. Docking predicts ligand binding orientation to form stable complexes. It identifies correct poses and binding affinities to aid hit identification and drug discovery. Popular docking software includes AutoDock, GOLD, Hex and SANJEEVINI.

1. PHARMACOPHORE MODELING
AND DOCKING TECHNIQUES
BY
KENCHA SWATHI
ASSISTANT PROFESSOR
DEPT OF PHARMACEUTICAL CHEMISTRY
ADITYA BIPER
BANGALORE

2. PHARMACOPHORE - INTRODUCTION
• A Pharmacophore model is the ensemble of common steric and electronic features that are
necessary to ensure the optimal molecular interactions with a specific biological target and to
trigger(or block) its biological response.
Definition: The schematic representation of nature of bioactive functional groups along with
their interatomic distance is known as a pharmacophore.

3. A pharmacophore represents molecular features as:
3D structure (Hydrophobic group,ionizable group,H donor or acceptor)
2D structure (substituents)
1D structure (Physical or biological properties)

5. TYPES OF DRUG DESIGN
1.Structure based: Pharmacophore modeling explains de novo drug design and
target identification.
2.Ligand based : Pharmacophore modeling includes virtual screening and lead
optimization.

6. STEPS INVOLVED IN PHARMACOPORE
MODELING
• All the algorithms for pharmacophore identification utilizes six steps
1.Input
2. conformational search
3.Feature extraction
4. structure representation
5. Pattern identification
6. scoring

7. APPLICATIONS
• Pharmacophore concept is used for rational drug design approach.
• It shows virtual drug screening strategy.
• It shows supramolecular interactions with the target an dgives an idea about blocking of biological
response.
• Lead optimization
• Multi-target drug design
• Pharmacological activity profiling
• Target identification.

8. VIRTUAL SCREENING STRATEGY

9. PHARMACOPHORE MODEL VALIDATION

10. DOCKING TECHNIQUES
Definition: Docking is an attempt to find the best matching between two
molecules. Docking is a method which predicts the preferred orientation of one
ligand when bound in an active site to form a stable complex.

11. • The receptor or enzyme or protein considered as a target and the lead drug is a
ligand.
• The protein can act as a lock and the ligand can act as a key.

12. TYPES OF DOCKING
• Rigid docking: The ligand and the target are in tight binding
• Flexible docking: In this type of docking ,the ligand and target are lightly binded.

13. • Docking can be between
PROTEIN - LIGAND
PROTEIN -PROTEIN
PROTEIN - NUCLEOTIDE

14. STAGES IN DOCKING
• Target/receptor selection and preparation
• Ligand selection and preparation
• Docking
• Evaluation of docking results.

15. IMPORTANCE OF MOLECULAR DOCKING
• Identification of the ligands correct binding efficiency (pose) in the binding site(binding
model)
• Prediction of the binding affinity
• Docking technique is essential in rational drug design.
• The molecular interactions between the drug or ligand and target or receptor can be found
easily.
• Virtual screening (Hit identification)
• The key step in Drug discoverey process

16. DOCKING SOFTWARES
• SANJEEVINI –IIT DELHI
• GOLD – CAMBRIDGE UNIVERSITY-U.K
• AUTODOCK – Scripps research institute ,U.S.A
• Hex PROTEIN DOCKING – U.K University of Aberdeen
• Gem DOCK – National Chiao Tung university, Taiwan

17. REFERENCES
• Pharmacophore modeling publications
• A textbook of computational Drug design by David C.Young
• Thomas Mavromoustakos textbook of rational drug design.
• PV publications Computer Aided Drug Design
• Journal of computational chemistry articles
• www.ncbi.nlm.nih.gov/pubmed/18446297