Bonding

Question 1

What are electrostatic interactions?

Ion

Answer 1

Attraction between molecules with opposite electronic charges.
It is also known as ion-ion interactions.

Question 2

What residues might be present on protein binding sites? And what interactions could they have?

Answer 2

CO2- and NH3+ may be present and they could interact with oppositely charged groups on the drug creating electrostatic interactions

Question 3

When are the electrostatic interactions strongest?

Binding site… hydrophobic

Answer 3

• They are typically strongest in a hydrophobic environment as there’s no competition.
• If you have water, other charged parts within the medium will compete for the interaction.
• Usually, the binding site is more hydrophobic than the surface so it will increase the electrostatic interactions.

Question 4

What is a dipole

Answer 4

A partial separation of charge

Question 5

What is hydrophobic effect 1?

Polar molecules

Answer 5

Polar molecules sit in polar environments and things which have no separation of charge (non-polar) will sit in less polar environments.

Question 6

What happens to entropy when a hydrophobic drug is placed into water?

Unfavoured

Answer 6

In its normal state water which is just flowing around is mainly disordered, so it will have high entropy (because it is disordered) If you introduce a non-polar molecule into it then the water which is surrounding the non-polar molecule will have to order itself a lot more than it would do otherwise. This means you have to reduce the entropy of the water because it has to arrange itself in a way to accommodate this molecule.
This is bad because the entropy has gone down, this is not a favoured thing to happen.
If the water could expel this hydrophobic effect that would be good and a favoured thing to happen.

Question 7

How do you overcome the hydrophobic effect?

Enthalpy

Answer 7

• You can add a protein in the solution so if the drug is fairly hydrophobic it won’t want to stay in the solution and would rather stay in the enzyme pocket and form a complex. This releases a lot of water which happened to be around each of these particular places.
• This increases the enthalpy of water and increases the chance of water forming hydrogen bonds which gives you an enthalpic benefit to forming a complex.
  If these two things fit together then the water isn’t going to get in and you can increase entropy to its maximum amount because you can expel the most water and also maximise the van der Waals interactions between these two things.
• If they fit together poorly then the water will still be going around and it won’t gain as much entropy

Question 8

How are entropy gains achieved in terms of the hydrophobic effect?

Active site

Answer 8

When water molecules are displaced from ‘active site’ and return to a more random state.

Question 9

How do you maximise van de waals?

Binding sites

Answer 9

• The molecules need to be fitted together as tightly as possible.
• This is important because the binding sites of proteins are normally hydrophobic so mutual attraction can occur.

Question 10

What drives the hydrophobic effect?

Answer 10

Entropy gains from van der waals bonding and from displacing the water.

Question 11

Why does pi stacking occur?

Stacking

Answer 11

• Due to efficient packing arrangement maximising dispersion interactions.
• Maximises van de waals and charges stacking upon one another.

Question 12

What does pi stacking in water do?

Stacking

Answer 12

It allows the hydrophobic things to stack and expel water efficiently.