CADD= represents computational methods and resources that are used to facilitate the design and

discovery of new therapeutic solutions.

- Emerging technology with less time and financial constraints. Helps computational chemist and
research scientists to design lead compounds for a specific disease.
Definition of drug, drug design. Criteria of the drug, characteristics, and function of drug.
Types of drug design
1) Ligand based DD- relies on knowledge of other molecules that bind to the biological target of
interest. Used to derive a pharmacophore (definition). Similarity searching and Pharmacophore
mapping. Uses principle of chemical or structural similarity of ligands. It can not find novel
class of hit/lead. Lesser chances of false positives.
2) Structure based DD- relies on knowledge of the 3D structure of the biological target obtained
through methods such as x-ray crystallography, NMR (Nuclear Magnetic Resonance). Drugs
that are predicted to bind with to the target may be designed using… via structure of the
biological target. Molecular docking. Uses principle of binding kinetics or interactions between
receptor and ligand. It can find novel class of hit/lead. Higher chances of false positives.
- Homology modeling- comparative modeling of protein, refers to constructing an atomic-
resolution model of the “target” and an experimental 3D structure of a related homologous
protein “template”
Steps of drug design
1) Selection of the disease
2) Target selection- enzymes, receptors, nucleic acids
3) Selection of ligands/drugs
4) Molecular docking- predicts the preferred orientation of one molecule to a second when bound
to each other to form a stable complex. Programs that can be used for molecular docking are
….
Benefits:
1) Time saving
2) Reduced cost
3) Improve quality of life
NEW VIDEO- Introduction to virtual screening
Typical screening- expensive (both money and time), can be automated but it still needs a lot of
human intervention, not all assays can be automated. Perform in vivo or in vitro depending on your
target compound.
Virtual screening- Cheap (saves both money and time), easily automated, dramatic reduction of the
number of compounds to test and false negative, enrich ligand libraries, allow to test in silico the
“druggability” of new targets.
Disadvantages= often inaccurate, scoring-function dependent, no method that’s better than others,
strongly depend on: (1) target, (2) search method, (3) fraction of chemical space sampled. Always
provides an answer.
- Search for compounds with a defined biological activity using a computational model. It is a
knowledge-based model. (Ligand-based/receptor-based)
- The goal is to identify a molecule able to bind to a target providing a biological function.
Autodock VS- analyze thousands of compounds
Looking for: A hit- low/medium target affinity, and lead- sub-optimal target binding affinity.
To be chosen for further development of a lead compound should have the following properties:
- Relatively simple chemical features (suitable for combinatorial/med-chem optimization, no/few
chiral centers)
 - Well-established SAR series (similar compounds/chemical groups should present similar
activity)
- Good ADME properties
- Favorable patient situation
Main steps in Drug design: