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CADD

Computer Aided Drug Design

Abhijeet KadamTSECBioTechnology

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Drug Working

● Interfere with biological function of viruses, bacteria etc

● Block their interactions with our system● Interfere or enhance our own biological system

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Keypoints

● Enzymes – lock and key model● Enzyme – Lock ● Keyhole – active site

● Receptor binds selectively to ligand● Ligand binding (imp factors)

– Steric– Electrostatic– Hydrophobic etc

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Drug Design Approach

● Ligand based● Structure based● De-Nova

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Ligand Based

● Receptor is not known● Done by 3 methods

– Database generation

– QSAR

– Pharmacophore

● Database generation – from ligand library– Needs structural information of ligand

– By combinotorial chemistry

– Find common characteristics of ligand

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Ligand Based

● QSAR – used when structure of ligand is not known

● Links between str-property of molecules● Checks

– Dimensions

– Physiochemical characteristics

● Helps decide which molecule can be active and can be selected for testing in-vitro.

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Ligand Based

● Pharmacophore – ● multiple L-R interactions points are available● Some are really important and suitable● Such sites are called pharmacophore● These sites are for structural integrity and

maximum activity

● To save time, first check all known pharmacophores and then the entire ligand.

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Structure Based

● Aka Direct DD● 3D structure is known – X-ray, NMR● Homology modelling – known str compared to

unknowns● In-vitro Testing for highly affinite and selective

ones

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De-Nova

● When no data about ligand available● Costomized ligand● Arrangement of H-bonds, donor/accpetor, hydrophobic etc● 2 types

– Outside In

– Inside Out

● 3 steps– Identify points on receptor

– Chose ligand's groups of atoms– Connect them on molecular frame

● ADME analysis – adsorption Distribution Metabolism Excreation

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De-Nova

● When no data about ligand available● Costomized ligand● Arrangement of H-bonds, donor/accpetor, hydrophobic etc● 2 types

– Outside In

– Inside Out

● 3 steps– Identify points on receptor

– Chose ligand's groups of atoms– Connect them on molecular frame

● ADME analysis – adsorption Distribution Metabolism Excreation