Principles of molecular recognition

Question 1

What are processes of life controlled by?

Answer 1

non-covalent molecular and recognition events

Question 2

How do 2 or more molecules recognise and communicate with each other?

Answer 2

In the case of similar geometrical structure, the molecues can approach each other so closely to initiate a chemical reaction. In order to exert this chemical effect, the enzyme and glucoside should fit together like a lock and key.

• Hermann Emil fischer

Question 3

What is the concept behind Fischer’s lock and key principle?

Answer 3

Recognition sites in the host (lock) are complementary to the sites on the guest (key)

Question 4

What is the induced fit?

Answer 4

Where enzyme active site or receptor biding domain does not necessarily need to be complementary to the drug or natural substrate. It is actually flexible and the fit is induced by presence of substrate or drug

Question 5

Can the induced shape change occur in the substrate or drug?

Answer 5

Yes

Question 6

What can the conformationally induced changes in shape be used to explain?

Answer 6

receptor function

Question 7

What are the 4 key non-covalent bonding interactions?

Answer 7

Ionic bond
Hydrogen bond
Van der waals bond
Coordinate bond

Question 8

What is the ionic bond?

Answer 8

~20kj/mol
Where a group on a substrate can attract an oppositely charged group.

The force of this electrostatic attraction is given by Coulomb’s law.

Question 9

What is the Hydrogen bond?

Answer 9

~7-40kj/mol
These form between both neutral and charged molecules where a hydrogen atom is “shared” between 2 other atoms.

The H bond donor is the atom where the H is more strongly bound.
The other atom is the H acceptor

Question 10

Which is the H bond donor in biological systems?

Answer 10

an O or N that possesses a covalently attached H atom

Question 11

What is the H bond acceptor in biological systems?

Answer 11

Either an O or N atom

Question 12

What is the van der waals bond?

Answer 12

~1.9kj/mol
This is a non specific attractive force that comes into play when any 2 atoms are 3-4 angstroms apart.
These are much weaker and less specific than either H bonds or electrostatic bonds.

they originate from the fact that the distribution of electric charge an atom changes with time- at any time the distribution of electron density is not symmetrical.

The transient asymmetry induces a similar and opposite perturbation in neighbouring atoms => attractive forces

Question 13

How does the strength of a VDW bond come about?

Answer 13

When many atoms in one molecule come close to other atoms of another molecule. This can only happen if the 2 molecules possess complementary 3D shapes.

I.e. we need both size and shape to be complementary

Question 14

What is the coordinate /dative bond?

Answer 14

Not strictly a non-covalent interaction.
This arises from the coordination of metals by ligands donating 2 Electrons to form a dative bond (Usually O, N, or S)

Typical examples: Histidine and Cysteine binding to Zn. The active site of carboxypeptidase A is based around a coordinated Zn atom

Question 15

What are covalent bonds?

Answer 15

The sharing of electrons. These are the strongest bonding forces available.

Question 16

Which is the only covalent bond that can contribute to tertiary structure of proteins?

Answer 16

The bond formed between SH groups on 2 cysteine residues.
This forms a disulfide bridge between two parts of the protein chain. This is more significant in small polypeptides like the hormones vasopressin and oxytocin.

Question 17

How is the S-S bond cleaved?

Answer 17

the bond strength is 250kj/mol. It cannot be cleaved thermally due to high bond energy, but can be cleaved reductively by excess of reducing agents like thiols

Question 18

What is the relative importance of bonding forces for tertiary structure of proteins?

Answer 18

Covalent (least important)< ionic< hydrogen< VDW

Question 19

Why are VDW bonds the most important for the tertiary structure of proteins?

Answer 19

There are more hydrophobic and polar amino acids than ionisable residues or cysteine residues so there is more opportunity for VDW interactions and H bonds

The hydrophobic effect occurs where amino acids at the surface of proteins interact with water. And water forms hydrogen bonds to polar amino acids like Serine.
water also forms ionic bondsto hydrophilic amion acids like Asparagine

Non polar amino acids are repelled by water (hydrophobic amino acids like glycine)

Question 20

What does the most stable tertiary structure of a protein have?

Answer 20

Hydrophilic groups on surface to interact withwater

Hydrophobic groups in centre so they can avoid water and interact with each other.

Question 21

Why s the number of ionic and hydrogen bonds contributing to the tertiary structure reduced?

Answer 21

Hydrophilic amimo acids can form ionic and hydrogen bonds to water

Question 22

Which interactions control the 3D shape of protein?

Answer 22

Interactions between the hydrophobic amino acids. These also outweigh the hydrophilic interactions