pharmacophore

1. Pharmachophore
Identification of pharmachophore
Abhijeet Kadam
TSEC
BioTechnology

2. Defination
● A pharmacophore is a specific 3D arrangement
of functional groups within a molecular
framework that are necessory to bind to a
macromolecule and/or an enzyme active site
● The identification of pharmacophore is
important step in understanding the interactions
between a receptor and a ligand

3. Pharmacophore
● Many possible iterations between ligand and receptor
● Depending on size of active, various steric-
electrostatic and hydrophobic contacts
● Some contacts or sites are more important than
others
● The specific interactions that are crucial for ligand
recognition and binding by the receptor are thermal
pharmacophore
● These interactions are directly involved in the
structural integrity of receptor or in the mechanism of
its action

4. Pharmacophore
● Pharmacophore model is derived from a set of
known ligands for a target
● Aslo using the set of features common to a
series of active molecules
● Features may include – acceptors, donors, ring
centroids, hydrophobes etc
● A 3D pharmacophore is used to define
relationships between groups or features

5. Pharmacophore
● Pharmacophore hypothisis are generated by the
multiple conformations of the set of molecules
● When protein is unknown, it is more efficient
● With the generated hypothysis, it is possible to
search the database for new hit compounds
● Searching the possible low energy conformations
of known inhibitors can identify pharmacophores

6. Different methods
● The conformation search can be quite large
and can be approaches using folowing methods
– Systematic search method
– Distance geometry method
– Clique detection algorithm

7. Systematic search method
● Generates sterically allowed molecular
conformations by systematically varying sets of
specified torsion angles
● Www.accelrys.com/cerius2/conformers.html

8. Distance geometry method
● Randomly samples conformations and are
particularly powerful for problems dealing with
molecular matching and flexibility
● Used by rubicon
● Www.daylight.com/products/rubicon.html

9. Clique detection algorithm
● Searhes common sets of inter feature distances
within the group of active molecules
● Tolerences on the distances matches aaccount
for the use of discret conformations and
uncertenties in pharmacophore
● Used by DiscoTech
● Www.tripos.com/scitech/insilicodisc/PharmaPer
ception/DiscoTech.html

10. Clique detection algorithm
● Searhes common sets of inter feature distances
within the group of active molecules
● Tolerences on the distances matches aaccount
for the use of discret conformations and
uncertenties in pharmacophore
● Used by DiscoTech
● Www.tripos.com/scitech/insilicodisc/PharmaPer
ception/DiscoTech.html