Computer Aided Drug Design: Rational Approaches in Medicinal Chemistry

Mr. Pulate Chetan Prakash, Assistant Professor, Department of Pharmaceutical Chemistry

Computer Aided Drug Designmeans In-Sillico techniques in the field of the Drug Design and Development. Itplays the important role in the drug discovery and development activity. Discovery and development is the very complex process but it is simplified and reduces the costing of the Practical work in laboratory with reducing valuable time also. Hence In-sillico techniques reduce time, money, manpower. The Major approaches in CADD include Structure based drug design and Ligand based drug design.Both these Direct acing and In-direct acting types respectively. The Structure based drug design related with identification of target which is protein. This is determined by X-ray, Crystallography, homology modeling and NMR Spectroscopy. Various chemical compounds Structures are interacted with biological protein on virtual screening method. By using this process the score and ranking is to be obtained on the basis of electrostatic, hydrophobic, steric interactions of these chemical structures with active site of the target protein. Finally those are to be top ranked and having the good scored only tested for Biological assays.

Target identification and validation is the initial step in it. Then it go for analysis structure for potential ligand sites. Molecular Docking shows the interaction between lead and receptor sites. After Validation and optimization of the compounds sends towards clinical trials. So various processes are to be done in case of structure based drug design. It appears to be most effective technique in case of drug design and discovery. It gives more potent drug candidates by reducing the unwanted properties such as poor efficacy, poor ADMET by using in silico filters.

In case of Ligand based drug design target protein structure is not known. On the basis of lead structure it should be known that where ligand to be bind on desired targetsite. In this way all possible modification are to be done to develop the phamacophore of molecule so is should possesses all required features for binding with target site. Ligand based technique is phamacophore based technique and Quantitative structure activity relationships method. Ligand based drug design shows that t hose structures having similarity in size and shape hey are showing the same biological action and interaction with target site. Molecular Docking is in-sillico method shows the interaction of molecule within the active site of their target protein and receptor.

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