RESP - C. QSAR-COVERED

Question 1

QSAR

Answer 1

• link with 2D or 3D molecular structure with biological activity
• predictive for new models
• ‘in silicon’ ie on a conpetitic
• ‘descriptors’ -how we describe a molecule with numbers

‘expressing biological activity as a function of molecular structure quantitively via molecular descriptors”

Question 2

what are molecule descriptors

Answer 2

a way of describing one aspect of a given molecule with a number of quantitative measures

Question 3

examples of simple molecular descriptors

Answer 3

number of atoms
molecular weight
number of c atoms
number of non-c atoms

Question 4

examples of more detailed molecular descriptors

Answer 4

sum of atomic polarisabilities
calculated logP (ie - lipophilicity)
topological eccentricity
shape of molecule
degree of branching
polar surface area
average hybridisation
number of aromatic groups
number of Lipinski rule of 5 failures

Question 5

classes of descriptors

Answer 5

1. 2D
   - limited stereochemical information
2. 3D
   - stereochemical information
   - dangerous? assumption molecular configuration known and is correct, doesn’t change

Question 6

Example: why are salmeterol, bambutamol, formeterol long lasting?
Can we link this with molecular structure via descriptors?

Answer 6

• list of B2 agonists taken from wikipedia
• SMILES codes captured
• 295 descriptors per molecule
• plot calculated descriptors
• think about extended action mechanism

*main mechanism controlling changes in duration: membrane affinity of drug
linked with fatty, oily, high MW molecules

Question 7

uni-variate

Answer 7

• 1 value of x (biological activity - cell assay, animal model) per value of y (molecular descriptors)

Question 8

multi-nucleate

Answer 8

• many values of y (molecular descriptors) per value of x (biological activity)

ie - football league table
x = league position
y = wins? wins and draws? points? goal-difference?

Question 9

QSAR process

Answer 9

1. collect data (for x and y)
2. build model linking x and y
3. test model
4. apply model to predict properties of new molecules so we can choose which one to synthesise

rational drug design