M. Pharm 2nd Sem Computer Aided drug delivery systems

1. An Introduction to Computer
Aided Drug Design
Dr. Rajan Swami
Assistant Professor
MMCP, MMDU

2. Drug Design
• TAILORING OF DRUG…but needed interdisciplinary approach.
• It is inventive process of finding new medications based on the
knowledge of a biological targets.
• It involves the design of a molecules that are complimentary in shape
and charge to the biomolecular target with which they interact and
therefore will bind to it

3. Life Cycle of Drug Design

4. Modern Drug Design
• Identification of target
• Verification of target
• Target selection
• Screen Development
• High Throughput Screening
• Secondary Assay
• Lead Exploration
• Potency in disease
• Pharmacokinetics
Target Selection Lead Optimization
Target Identification Final

5. Drug Designing…
• Selected/Designing molecules should be:
• Organic Small Molecules
• Complementary in shape to the target
• Oppositely Charge to the biomolecular target
• There are various parameters which have to be considered in
designing of drugs; drug should be:
• Safe and effective
• Bioavailable
• Metabolically stable
• Minimal side effects
• Selective target tissue distribution

6. Drug Designing…
• This Molecule will:
• Interact with target
• Bind to the target
• Activates or inhibit the function of a biomolecules such as a protein

7. Drug Designing…
• Drug Design frequently but not necessarily relies on computer
modelling techniques.
• This type of modelling is sometimes referred to as Computer-Aided
Drug Design.

8. Drug Discovery and Development

10. CADD
• The implementation of computer based techniques to accelerate and
bring about precision in drug designing and drug developmental
process.
• Prediction tool to screen the active constitutent.
Early 1990
Extraction Isolation Purification
Biological
testing

11. CADD

12. Objective of CADD

13. Significance of CADD
• Filtration of large compound libraries into smaller compounds sets of predicted
activity those could be further tested experimentally.
• Gives information about optimization of lead compounds, whether to increase
bio affinity and pharmacokinetic properties like absorption, distribution,
metabolism, excretion (ADME) as well as toxicity knowledge.
• Designing of novel compounds containing one functional group in a chemical
compound or new chemo types by joining different fragments

14. Types of Drug Design

15. Ligand Based Drug Design (Indirect)
• Existing molecule mimicking
• Do not have receptor 3 dimensional data
• Structure derived from Pharmacophore model that defines the minimum
necessary structure characterises a molecule must posses in order to bind to
target/receptor.
Alternatively, a quantitative structure activity
relationship (QSAR), in which a correlation
between calculated propertied of molecules
and their experimentally determined biological
activity, may be derived. These QSAR
relationship in turn helps to predict activity of
new analogues.

16. Cont..

17. Homologous Modelling (comparative
modelling of protein)
• When crystal structure is not known
• Make structure based on aminoacid sequence or template alignment.
• Friends home (Receptor)------Sofa (Ligand-Drug)
Mutant Strains can be studied (Covid, HIV etc)
1
2

18. Structure Based Drug Design (Direct Method)

19. Structure bases drug design cont..

20. Methods

21. Binding Site Identification

22. Docking and Scoring

23. Component of Docking

24. Advantages of CADD
• Time
• Cost
• Accuracy
• Information about disease
• Screening is reduced
• Database screening and makeup
• Less manpower is required

25. In silico Drug Discovery Process
Consists of 3 Stages
• Stage 1: Identification of therapeutic target and
• generation of small compounds library for the testing and
screening against the target molecule.
• Stage 2: Interaction testing of selected hits by docking at
the binding sites.
• Stage 3: Subjection of selected compounds to
pharmacokinetic studies and the compound that passes
the pharmacokinetic parameters is used as a lead
compound

26. Approaches used in Drug designing using CADD
A) Known 3-D structure of protein

27. B) Structure of 3-D protein is not known (For new
molecules)

28. Unknown Target
• Examination of QSAR, potency, docking and scoring, multi regression
analysis.
• Reactivity evaluation like nucleophilic, electrophilic
• Evaluation of in-vivo experiments, bioinformatics analysis, etc.
• Preclinical evaluation

29. Thank you