L19 QSAR Analysis DB

Question 1

The solubility and partitioning behaviour is summarised using what?

Answer 1

Log P value.

Question 2

Steric props are quantified how?

Answer 2

VDW

Question 3

VDW is used to

Answer 3

quantify steric properties

Question 4

LogP value is used for

Answer 4

summarising the solubility and partitioning behaviour.

Question 5

Hammetts constants summarise

Answer 5

how the charge distribution of the compound is influenced by e- withdrawing/donating groups

Question 6

comment on correlation coeffient

Answer 6

the correlation coefficient, R, is a measure of the strength and direction of the linear relationship between two variables that is defined. It can however give a misleading impression of the reliability of a QSAR model. This is because the R would naturally tent towards 1.0 as the regression coefficients used in the QSAR equation increases.

We therefore need to look at other statistical parameters to judge which type of our QSAR models/equation is best for predicting activity.

Question 7

the letters within the brackets e.g (+- 0.22) symbolise

Answer 7

the % error.

Question 8

F statistic measures

Answer 8

explained variance/unexplained variance.

Question 9

100.Pa gives

Answer 9

gives the probability that the F value could have arisen purely due to chance.

Question 10

what size should Pa be?

Answer 10

sould be small as it measures the reliability of the equation

Question 11

What groups make better inhibitors?

Answer 11

electron withdrawing groups

Question 12

If two physico-chemical properties are sighted to have a high correlation what do you do?

Answer 12

Generally you would not use both properties in Hansch analysis equation.

e,g LogRb = K1.logP + K2.V + K3

instead use:
LogRb = K1. logP + V3

Question 13

What is Ki a measure of and discuss its magnitudes

Answer 13

Ki is a measure of inhibitor. Smaller Ki means a more potent inhibitor, so 1/Ki -> bigger number so better inhibition.

Question 14

State the ideal relationship between F and Pa

Answer 14

IF F value is large and Palpha is very small (e.g 1.0*10^-8 then this means there is greater confidence that the model explains the data in a more meaningful way

Question 15

outline the principle of qsar mathehatical equations

Answer 15

1. Set up equations with appropriate constants for each compound
2. Perform multiple regression analysis to obtain best fitted values
   for the regression coefficients, k1, k2
3. Assess the significance of different parameters / molecular properties
4. Optimise the design of the active molecule