Ligand based drug design

Question 1

thermodynamic ligand binding reaction

Answer 1

Question 2

Relation of Gibbs free energy to binding affinity

Answer 2

• Logarithmic relationship between free energy and binding affinity implies that an increase in G of 6.3 kj/mol results in an aproximately 10 fold increase in binding affinity, apriximating the strength of a gas phase O-H..N bond.

Question 3

Application of ligand based drug design

Answer 3

• precise nature of the target is not known
• no 3D structure of the protein is available
• 3D structure of the protein but ligand binding mechanism is not known

Question 4

interactions which control drug binding to proteins

Answer 4

1. Electrostatic (coulombic, long range > 10 A)
2. VDV (short < 5)
3. H bonds (Short 1-5 A)
4. Steric (short)
5. Hydrophobic (short )

Question 5

Use of pharmacophores in screening

Answer 5

• Computational pharmacophores can be used to find additional compounds that contain the required phamacophore groups in a simmilar 3D arrangement
• Virtual hits can be synthesized/purchased and tested in real assays