principle of drug designing

8/7/2019 PRINCIPLE OF DRUG DESIGNING

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niTza Biologicals April,2007

Enriching Bio-Science .












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PRINCIPLES OF DRUG DESIGNING

DRUG DISCOVERY PROCESS

1) Target Identification.

2) Target Validation.3) Lead Identification.

4) Lead Optimization.

5) Preclinical Pharmacology & Toxicology


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WHAT ISADRUG ?

Drug is a molecule that designed to bind, interact or

to modulate the action of specific biological receptor;

The Biological Receptor may be a cell surface receptor

(Hormone receptor, Neurotransmitter receptor) or may

be any enzyme whose activity has been altered by any

physiological stresses or due to genetic abnormalities, etc.


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PROPERTIES OFAN IDEAL LIGAND

Steric complementarity

Physico-chemical complementarity

Electrostatic complementarity

Hydrophobic interactions


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MAINAPPROACHES OF DRUG DESIGNING

1) Ligand basedApproaches :-(a) Ligand Unknown :-

- Combinatorial Chemistry used to generate a large

libraries of molecules which can be screened for

biologically active compound.

(b) Ligand Known :-

- a set of active ligand molecules is known for themacromolecular target but a little information

exist for the target.


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Ligand Known :-

1) QSARMethod :-

It involves the statistical analysis of a set of properties or

descriptor for a series of biologically active molecules.

The Statistical model developed then is used to predict

the activity of additional compounds against the target.

eg., Mol. Wt., Volume, Solvent Accessible Surface Area,

Mol. Interaction field.


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2) PharmacophoreModel :-

Depending upon the size of the active site there

may be numerous Steric, electrostatic & hydrophobic

interactions.

The specific interactions that are crucial for the ligand

recognition and binding by the receptor are termed asPharmacophore.


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2)Target basedApproach :-

(a) Ligand known :-

- Docking :- It involves scanning a database of knownmolecules for those likely to bind well to the receptor.

It generate possible binding geometry for each

molecule and evaluate the score for each.


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(b) Ligand Unknown :-

- De novo designing :-

Used to build a customized ligand for a given receptor.

Identify favourable interaction points on receptor.

Choose complementary groups.

Connect them into a molecular frame work.

- Receptor based 3D searching


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Protein-Drug Interaction

Mechanism of

Drug Action:

A drug interferes withthe function of a

disease protein bybinding to it.

This interferencestops the diseaseprocess

Drug Design:

Structure of diseaseprotein is very useful


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Protein-Drug Interaction

Mechanism of

Drug Action:

A drug interferes withthe function of a

disease protein bybinding to it.

This interferencestops the diseaseprocess

Drug Design:

Structure of diseaseprotein is very useful


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DRUG DESIGNING SOFTWARES

AutoDock

Dock

LUDI LEGEND

Hook

HYPERCHEM


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Drug Design CycleDrug Design Cycle


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TH NK YOUTH NK YOU


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principle of drug designing

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