PPIs

Question 1

Describe the trends of interactions in PPIs.

Answer 1

Correlation between number of H bonds and interface SA.

No correlation between number of salt bridges and interface size.

Question 2

What types of AAs are preferred at PPI interfaces and what types are preferred in IDPs?

Answer 2

PPI = small preference for arg residues (Tyr in Abs)

IDPs = low content bulky hydrophobic AAs - high in simple and charged.

Question 3

How do IDPs pay the entropic penalty associated with binding?

Answer 3

as lack hydrophobic residues to make hypho core, they form H bonds with water (rather than intramolecular)
On binding pay entropic penalty by energy of molecular interaction.

Question 4

What special molecular recognition features do IDPs have?

Answer 4

• short interaction motifs
• coupled folding & binding
• large SA gives high SPECIFICITY without high AFFINITY –> dynamic but specific intercatiosn.
• fly casting
• fuzzy complexes where interfaces have high degree of disorder.

Question 5

Give an example of why studying PPIs is useful.

Answer 5

Chronic myeloid leukaemia
95% of cases caused by Abl kinase over expression, inappropriately phosphorylates targets

Inhibited by glivec - fitting into AS and inhibiting activity.

Question 6

How many AAs tend to feature at an interface?

Answer 6

34 +- 7 for antibody antigen complexes

Question 7

What trend can be seen in electrostatics?

Answer 7

No trend as half complexes have no ionic interactions .

Question 8

What are the main features used to characterise PPIs?

Answer 8

Size

No of residues at interface

H bonding / electrostatics

Types of AAs

Conformational changes

Packing shape.

Question 9

What are the ranges in energies of G and Ka changes ?

Answer 9

• 29.2 to -71.9
  1. 3 X 10e5 to 4 X 10e12

More enthalpic drive pay higher entropic penalty.

Question 10

What are the H and TS changes associated with PPIs?

Answer 10

52. 6 to -278.8

97. 8 to -237