MEDICINAL CHEMISTRY - DRUG DESIGN - PHARMACOPHORE MODELING AND DOCKING TECHNIQUES

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