S TRUCTURAL B IOINFORMATICS

A subset of Bioinformatics concerned with the of biological structures - proteins, DNA, RNA, ligands etc. It is the first major effort to show the application of Bioinformatics on Macromolecular structure prediction, How macromolecules carry out cellular functions, How bioinformatics can improve health care system by accelerating diagnostic procedure of diseases and drug discovery.

D ISCOVERY A ND D ESIGN OF D RUGS Traditional Methods Modern Method of Drug Discovery/ Rational Drug Design

It is one of the most promising area of application for Bioinformatics research. The process of drug discovery involves Identification, Synthesis, Characterization, Screening, and Assay of candidates for therapeutic efficacy. So this is the end-to-end process of designing pharmaceutical agents to prevent and/or cure human disease S TRUCTURAL B IOINFORMATICS IN D RUG D ISCOVERY

I NTERESTING FACTS... Over 90% of drugs entering clinical trials fail to make it to market The average cost to bring a new drug to market is estimated at $770 million

I MPACT OF S TRUCTURAL B IOINFORMATICS ON D RUG D ISCOVERY Speeds up key steps in Drug discovery process by combining bioinformatics, structural biology, and structure-based drug design

I DENTIFYING T ARGETS

Human Genome polysaccharides lipids nucleic acids proteins Toxicity, specificity and difficulty in designing Potent Inhibitor……eliminate Polysaccharides Lipids Nucleic acids

Human Genome proteins P roteins with Binding Site Protein: Ion channels Receptors Enzymes

R ELATING TARGETS TO DISEASE... Analysis of Pharma industry reveals: Over 400 proteins used as drug targets Sequence analysis of these proteins shows that most targets fall within a few major gene families (GPCRs- Guanine Nucleotide Binding-Protein Coupled Receptors, kinases, proteases and peptidases) Fig. Fauman et al.

Drug Design Structure based Ligand based

Ligand (analog) based drug design Receptor structure is not known Mechanism is known/ unknown Ligands and their biological activities are known Target (structure) based drug design Receptor structure is known Mechanism is known Ligands and their biological activities are known/ unknown

B RINGING A N EW D RUG TO M ARKET Review and approval by Food & Drug Administration 1 compound approved Phase III: Confirms effectiveness and monitors adverse reactions from long-term use in 1,000 to 5,000 patient volunteers. Phase II: Assesses effectiveness and looks for side effects in 100 to 500 patient volunteers. Phase I: Evaluates safety and dosage in 20 to 100 healthy human volunteers. Discovery and preclininal testing: Compounds are identified and evaluated in laboratory and animal studies for safety, biological activity, and formulation. 5,000 compounds evaluated Years 16 Source: Tufts Center for the Study of Drug Development