strategies of protein protein interactions

1. S.Prasanth Kumar, Bioinformatician Proteomics Protein-Protein Interactions S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA www.facebook.com/Prasanth Sivakumar FOLLOW ME ON ACCESS MY RESOURCES IN SLIDESHARE prasanthperceptron CONTACT ME [email_address]

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 ( Δ ASA) when going from a monomeric form to dimeric form Size and Shape Measured in ˚A Δ ASA method A correlation between the hydrophobic free energy of transfer from polar to a hydrophobic environment and the solvent ASA Calculating Δ ASA may provide a measure of the binding strength

7. Protein-Protein Interfaces The mean Δ ASA on complexa (going from a monomeric state to a dimeric state) was calculated as 1/2 ( Δ ASA of Protein Interface Unit 1) + ( Δ ASA 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 C α positions, where n is taken as the number of residues observed in the known homodimer interface Unknown Structure Known Structure n C α atom Contiguous amino acids

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