Rational Drug Design

Question 1

What are the limitations of X-ray crystalography

5 points

Answer 1

1. Target may be unknown/may not crystallise
2. The structure may have been incorrectly fitted to the electron density (rate)
3. The electron density may not have been correctly interpreted
4. Crystallisation conditions may have affected the protein-ligand interactions
5. The resolution may be insufficient for drug design

Question 2

What factors are to be considered with binding?

4 points

Answer 2

1. Strain energy
2. Translational/rotational energy
3. Ligand configurational entropy
4. Solvent entropy

Question 3

Binding - Strain Energy

Why is there an increase in strain energy upon binding?

Answer 3

Ligand and protein commonly change shape upon binding to optimise protein-ligand energy causing a change in internal energies

Question 4

What types of selectivity are there

5 points

Answer 4

1. Shape
2. Electrostatic
3. Flexibility
4. Hydration
5. Allostery