Drug-target bonds

Question 1

Give features of proteins?

Answer 1

• Proteins are made of strings of amino acids joined together by peptide bonds
• Most proteins are folded (tertiary structure)
• Proteins can move (channels can open and close, receptors can activate, G-protein subunits can separate)
• Proteins are dynamic structure
• Proteins exist in solvents

Question 2

What do drugs do with the binding domain?

Answer 2

• Drugs make specific connections (bonds) with binding domain
• Binding energy of drug -> conformational effect

Question 3

What are the dynamics of Nramp?

Answer 3

• Natural resistance associated macrophage protein
• Involved in defence against intracellular pathogens
• Ion transporter
• Secondary structure moves around quite a lot due to thermal agitation of the protein

Question 4

Myoglobin is a water soluble protein - what does this mean?

Answer 4

• Water molecules form a hydration shell around

- Interact positively with (Mb)

Question 5

What happens with Glutamine binding to GBP?

Answer 5

• Starts in open state with cleft in middle
• When glutamine interacts pulls two amino acids together and closes the cleft
• Makes a much more compact shape

Question 6

Give features of binding domain topology

Answer 6

• Often folding brings amino acids that are far away in the linear structure close together
  = binding domain can involve linearly distant amino acids
• This can help form a binding domain
• The peptide backbone is a very important component of the binding domain – they help shape it and provide the chemical environment
   Full of nitrogen and oxygen which are very important in some bond types
   Helps form structure

Question 7

What are some polar amino acids?

Answer 7

 Serine
 Cyesteine
 Threonine
 Glutamine
 Asparagine

Question 8

What are some acidic amino acids?

Answer 8

 Glutamate

 Aspartae

Question 9

What are some Aromatic amino acids?

Answer 9

 Phenylalanine
 Tyrosine
 Tryptophan

Question 10

What are the nonpolar amino acids?

Answer 10

 Alanine 
 Glycine
 Leucine
 Isoleucine
 Valine
 Proline
 Methionine

Question 11

What are the basic amino acids?

Answer 11

 Lysine
 Arginine
 Histidine

Question 12

What are ion-dipole bonds?

Answer 12

Between an ion and a dipole

Question 13

What are dipole-dipole bonds?

Answer 13

Between two dipoles

Question 14

What are ionic bonds?

Answer 14

 Strongest type of bond 
 > 100 KJ/mol 
 Holds together salt 
 Not very common 
 Between oppositely charged ions

Question 15

What is a dipole?

Answer 15

A partially charged atom

Question 16

What do you need for a hydrogen bonds and give examples of these and how they work?

Answer 16

• You need a hydrogen bond acceptor and a hydrogen bond donor
• A hydrogen bond acceptor is usually an oxygen or nitrogen bonded to a carbon
• Key features of nitrogen and oxygen that make them H bond acceptors is that they are electronegative and have a lone pair of electrons
• In hydrogen bond donors you have an Oxygen, Nitrogen or Sulphur bonded to a hydrogen
• Here the electronegative atom tries to steal the electron it shares with the hydrogen – this leaves the hydrogen with a slight positive charge (it becomes a dipole)
• The partially positive hydrogen will interact with the nitrogen or oxygen’s (the acceptor’s) lone pair of electrons. This is a dipole-dipole interaction. This can be fairly strong

Question 17

Give features of hydrogen bonds

Answer 17

• Directional
• (linear>angled)
• 4-20 KJ/mol
• Maximum bond strength of hydrogen: 20-30 KJ/mol
• key to secondary structure of the protein (alpha helices and beta pleated sheets)

Question 18

What are hydrophobic bonds?

Answer 18

• they are formed by entropy gain when two hydrophobic regions come together to hide from water
• it increases the disorder of the system

Question 19

What is the simulation of a solvated protein?

Answer 19

• Protein will have arranged itself so that hydrophilic bits face out and interact with water
• Hydrophobic bonds buried in the middle – hold protein together

Question 20

What are Van der Waal bonds?

Answer 20

• General attraction between two molecules
• Local dipoles – electrons randomly arrange themselves (not because the molecules are polar)
• Very weak <2 KJ/mol
• In the dipole they will have a partially positive and partially negative charge

Question 21

What are covalent bonds?

Answer 21

• Very strong (>100 KJ/mol)
• Full electron sharing
• Quite rare

Question 22

What drugs use covalent bonds?

Answer 22

Irreversible enzyme inhibitors (organophosphates, aspirin)