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strategies of protein protein interactions
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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
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All mers - Homodimer
subunit A subunit B
All mers – Protein-Small Molecule Interaction
e.g. Enzyme-Inhibitor Complex
Trypsin Protein
Inhibitor
All mers – Heterodimer
e.g. Antibody-protein complex
Fab Light Chain
Fab Heavy Chain
Lysozyme
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 individualmonomer structures.
KEY POINT
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 transferfrom polar to a hydrophobic environment and the solvent ASA Calculating ΔASA may provide a measure of the binding strength
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 themolecular weights of the constituent subunits
For heterocomplexes, MW of smaller subunit taken into account since its interface is less
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 acomplex was analyzed by calculating
The rms deviation of all the interface atoms
Planarity
Mannose binding protein
Non-Planarity or Twisted
Isocitrate dehydrogenase
Complementarity Between Surfaces.
Electrostatic and the shape complementarity observed between associating molecules
Gap index (A) =
gap volume between molecules (A3)/interface ASA (A2) (per complex)
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 (AAj) 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.
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
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 atomContiguous amino acids
Thank You For Your Attention !!!
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