Protein protein interactions

strategies of protein protein interactions

1. S.Prasanth Kumar, S.Prasanth Kumar,
BioinformaticianBioinformatician
Proteomics
Protein-Protein InteractionsProtein-Protein Interactions
S.Prasanth Kumar
Dept. of Bioinformatics
Applied Botany Centre (ABC)
Gujarat University, Ahmedabad, INDIA www.facebook.com/Prasanth Sivakumar
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2. All mers - Homodimer
subunit A
subunit B

3. All mers – Protein-Small Molecule Interaction
e.g. Enzyme-Inhibitor Complex
Trypsin
Protein
Inhibitor

4. All mers – Heterodimer
e.g. Antibody-protein complex
Fab Light Chain
Fab Heavy Chain
Lysozyme

5. Stressing Factors
Hydrophobicity, accessible surface area, shape, and residue
preferences between interior, surface, and interface
components
Prediction of interface sites using residue
hydrophobicity.
Most homodimers are only observed in the multimeric state,
and it is often impossible to separate them without
denaturing the individual
monomer structures.
KEY POINT

6. Protein-Protein Interfaces
Calculate solvent accessible surface area (ΔASA) when going
from a monomeric form to dimeric form
Size and Shape
Measured in ˚A
ΔASA method
A correlation between the hydrophobic free energy of transfer
from polar to a hydrophobic environment and the solvent ASA

Calculating ΔASA may provide a measure of the binding
strength

7. Protein-Protein Interfaces
The mean ΔASA on complexa (going from a monomeric state to a
dimeric state) was calculated as
1/2 (ΔASA of Protein Interface Unit 1) + (ΔASA of Protein
Interface Unit 2)
+ ……
To find how much of a protein subunit's surface is buried on
complexation
the AASA value for individual complex were compared with the
molecular weights of the constituent subunits
For heterocomplexes, MW of smaller subunit taken into account
since its interface is less

8. Planarity
To assess how flat or how twisted the protein-protein
interfaces
A measure of how far the interface residues deviated from
a plane (termed planarity) was calculated
The planarity of the surfaces between two components of a
complex was analyzed by calculating
The rms deviation of all the interface atoms

9. Planarity
Mannose binding protein

10. Non-Planarity or Twisted
Isocitrate dehydrogenase

11. Complementarity Between Surfaces.
Electrostatic and the shape complementarity observed
between associating molecules
Gap index (A) =
gap volume between molecules (A
3
)/
interface ASA (A
2
) (per complex)

12. Residue Interface Propensities
The relative importance of different amino acids residues in
the interfaces of complexes can give a general indication of
the hydrophobicity
Residue interface propensities were
calculated for each amino acid (AA
j
)
as the fraction of ASA that AA-
contributed to the interface
compared with the fraction of ASA
that AA. contributed to the whole
surface (exterior residues +
interface residues)
A propensity of >1 denotes that a
residue occurs more frequently in
the interface than on the protein
surface.

13. Hydrophobicity Including Hydrogen Bonding
Proteins will associate through hydrophobic patches on their
surfaces. However, polar interactions between subunits are
also common
The homodimers rarely occur or function as monomers,
and hence their hydrophobic surfaces are permanently
buried within a protein-protein complex

14. Patch Analysis of Protein Surfaces in Homodimers
A patch is defined as a central surface accessible residue
with n nearest surface accessible neighbors, as defined by
Cα positions,
where n is taken as the number of residues observed in the
known homodimer interface
Unknown Structure
Known Structure
n
Cα atom
Contiguous amino acids

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