Shape and interactions in drug design

Question 1

What is meant by dispersion energy?

Answer 1

Interaction between any atoms/molecules A and B which both have electron clouds

Question 2

What does dispersion energy depend on?

Answer 2

polarisabilty

Question 3

Dispersion energy is always favourable. True or false?

Answer 3

True

Question 4

Repulsion energy is always unfavourable true or false?

Answer 4

True

Question 5

How do you calculate the total interaction energy?

Answer 5

Add together the dispersion energy and the repulsion energy

Question 6

What is the conformational energy change?

Answer 6

the energy penalty required to change ligand conformation when it binds

Question 7

What is glaucoma?

Answer 7

Progressive degeneration of the optic nerve - specifically the ganglion cells

Question 8

Is glaucoma age related?

Answer 8

Yes

Question 9

Glaucoma is the second leading cause of blindness worldwide, True or false?

Answer 9

True

Question 10

How can glaucoma be diagnosed?

Answer 10

Examine optic nerve - vision loss not usually discovered till disease is advanced
Examine vision - loss of peripheral vision

Question 11

How can glaucoma be treated?

Answer 11

Surgery - excise small portion of eye to enhance drainage of aq humor
Laser - direct light to back of eye to enhance drainage
Drugs..

Question 12

What drugs can be used to treat glaucoma?

Answer 12

B-blockers and carbonic anhydrase inhibitors - reduce aq secretion

Question 13

Glaucoma is linked to increase pressure of ______ in the eye (intraocular pressure)

Answer 13

fluid

Question 14

Production of HCO3- is linked to production of aq humor. True or false?

Answer 14

True

Question 15

Which element do carbonic anhydrase enzymes depend on?

Answer 15

Zinc

Question 16

How many different carbonic anhydrase isozymes are there in the body?

Answer 16

14

Question 17

Which carbonic anhydrase isozymes are found in the eye?

Answer 17

CA 2 and CA 4

Question 18

Which drugs are a major class of carbonic anhydrase inhibitors?

Answer 18

Sulfa drugs

Question 19

How do sulfa drugs inhibit carbonic anhydrase?

Answer 19

they bind directly to Zn2+ at the base

Question 20

Carbonic anhydrase is coordinated by which three histamine residues?

Answer 20

His94
His96
His119

Question 21

Why is carbonic anhydrase hard to target?

Answer 21

Because it is found all over the body not just in the eye

Question 22

It is desirable to target the eye directly (topically) so all carbonic anhydrase inhibitors that exist are topical. True or false?

Answer 22

False - none of existing CAIs reduce IOP when given topically due to wrong physiochemical properties