COMPUTER AIDED
DRUG DESIGN
Dr. Sarmistha Saha
Assistant Professor
Department of Biotechnology 1
Drug Discovery
• a process by which the drug candidate is identified and partially validated for the treatment
of a specific disease.
1. Mechanism of action
2. Target identification/validation
3. Lead identification/optimization
4. ADME properties
5. PK/PD studies
6. Toxicity
• Drug discovery doesn’t include
• Preclinical studies
• Clinical trials Drug Development process
• Regulatory approvals
• Sales and marketing
Drug discovery and development
The discovery phase The development phase
Pre-discovery Pre-clinical testing
Gather as much information as possible about the disease In vitro and in vivo testing to determine if the drug is safe enough for
and try to understand its nature. human testing.
Target identification Clinical trial exceptions (CTX) applications
Choose a molecule in the body to target with a drug; often a File CTX with appropriate authorities before clinical testing can begin.
protein.
Phase 1 clinical trial
Target validation Initial human testing in a small group of healthy volunteers.
Test the target and confirm its role in the disease.
Phase 2 clinical trial
Drug discovery Test in a small group of patients.
Find a promising molecule (a ‘lead compound’) that could
become a drug. Phase 3 clinical trial
Test in a large group of patients to show safety and efficacy.
Early safety tests
Initial tests on lead compounds, including pharmacokinetics, Marketing authorisation application
by experiment and/or computer modelling. Apply to appropriate authorities for approval.
Lead optimisation Manufacturing
Alter the structure of lead candidates to improve properties; Begin full-scale production.
this may include formulation, delivery mechanism and scale-
up. On-going studies and Phase 4 trials
Continuing monitoring and checking of the drug in use.
New Drug Approvals: 1989 to 2000
Drug Designing
1. Ligand-based
2. Target- based
Ligand-based drug design (or indirect drug design) relies on knowledge of other molecules that bind to the biological
target of interest.
These other molecules may be used to derive a pharmacophore model that defines the minimum necessary structural
characteristics a molecule must possess in order to bind to the target.
Structure-based drug design (or direct drug design) relies on knowledge of the three dimensional structure of the
biological target obtained through methods such as x-ray crystallography or NMR spectroscopy.
If an experimental structure of a target is not available, it may be possible to create a homology model of the target
based on the experimental structure of a related protein.
Using the structure of the biological target, candidate drugs that are predicted to bind with high affinity and
selectivity to the target
Current Drug Discovery approach
Target based approach: identifying & validating small compounds that have specific activity against a specific
target (protein or enzyme) whose function is essential for disease phenotype.
