1. Genomics & Proteomics Based Drug DISCOVERY Dr. Basavaraj K. Nanjwade M.Pharm., Ph. D Associate Professor Department of Pharmaceutics KLE University BELGAUM – 590010

5. Genome Sequencing C = Cytosine, G = Guanine, A = Adenine and T = Thymine

13. Genome Annotation and Analysis

14. Impact of Structural Bioinformatics on Drug Discovery . Speeds up key steps in DD process by combining aspects of bioinformatics, structural biology, and structure-based drug design

15. human genome polysaccharides lipids nucleic acids proteins Problems with toxicity, specificity, and difficulty in creating potent inhibitors eliminate the first 3 categories...

16. “ druggable genome” = subset of genes which express proteins capable of binding small drug-like molecules human genome polysaccharides lipids nucleic acids proteins proteins with binding site

18. Proteomics

19. Process Flow Chart of Proteomics (Image) analysis (Data massage, Evaluation) Spot identification (Mass spectrometry) Biomarkers (Principal compound analysis) Two dimensional – gel electrophoresis

24. Protein-Ligand Docking Starting orientation of the program with 2 water molecules as the “Protein” and “Ligand” (a useful setup for testing the application). The energy of the system is in J/mol.

25. Protein-Ligand Docking Independent control of both molecules is allowed. The leftmost molecule is rotated using a trackball style rotation, while the second molecule remains fixed.

26. Protein-Ligand Docking From the previous figure, the second molecule has been independently translated up and away from the first molecule. Molecules can be arbitrarily positioned and oriented in 3D

27. Protein-Ligand Docking This is the same setup as the previous figure, except the viewpoint has been rotated, translated and zoomed to a different location. The energy of the system remains the same as the molecules are physically unmoved relative to each other

28. Protein-Ligand Docking The two oxygen atoms are just overlapping and consequently the energy of the system takes on a large negative value indicating a VERY high energy (the energy well is reversed for the purpose of the program, so large positive values indicate a favourable conformation, and large negative values indicate unfavourable conformations

29. Protein-Ligand Docking Here the atoms are at an optimum distance for the van der Waals Forces to hit the minimum of the well potential. However, the atoms are not aligned for any dipole-dipole interaction or hydrogen bonding

30. Protein-Ligand Docking The energy of the system attains a maximum with the following orientation. This is the orientation that occurs between water molecules when ice forms. This puts the hydrogen bond in its optimum orientation, and this changes makes another order of magnitude difference in the energy of the system