04236nam a2200289 a 450000100080000000500110000800800410001910000220006024501240008226001800020630000190038650000190040552032360042465000190366065000140367965300200369365300200371365300490373365300480378265300120383070000210384270000170386370000150388070000160389570000190391170000160393015762652020-01-15       2009    bl uuuu     u00u1 u    #d1 aNESHICH, I. A. P.  aSurface hydrophobicity index (SHI)binsight into the mechanisms of protein-protein associations.h[electronic resource]  aIn: INTERNATIONAL CONFERENCE OF THE BRAZILIAN ASSOCIATION FOR BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, 5., 2009, Angra dos Reis. Abstracts book... Angra dos Reis: ABBCBc2009  aNão paginado.  aX-Meeting 2009  aIt is widely accepted that hydrophobic interaction (HI), the effective attraction between nonpolar (sub)molecular groups in water, play a central role in protein folding leading to stability of protein structures. In addition, the HI is also supposed to be related with formation of protein complexes, where molecular association involves entropy loss of the subunits and entropy gain of solvent. Janin and coworkers have estimated such (unfavorable) entropic cost at 20-30 kcal/mol and suggested that the burial, upon complexation, of exposed hydrophobic surface area is the main force for oligomerization (because it increases water entropy). This conclusion is supported by analyses first done by Argos and colleagues, which revealed that interface region of monomers has also been found to be more hydrophobic than the rest of solvent-exposed surface. Interested on properties, in particular into the hydropobicity, of protein surface in complexes and their isolated subunits, we decided to introduce a parameter, derived from the known scales (such as Kyte-Doollittle, Eisenberg and Engelman), normalizing aminoacid Hydropathy by their effective accessible surface area: the Aminoacid Normalized Hydrophobicity Index (ANHI). The accessible surface area per residue is calculated using SurfV program. In addition, we created a new parameter reported in a "per chain? fashion: Surface Hydrophobicity Index (SHI). SHI describes the cumulative surface Hydrophobicity for a selected chain in two flavors: isolated chain and chain in complex with another chain. SHI is calculated as the sum of all normalized ANHI of Hydrophobic (HB) residues (i.e. the aminoacids with positive values of Kyte-Doollittle hydropathy scale) divided by the sum of ANHI of all Hydrophilic (HL) residues of a PDB chain (SHI = ΣANHIHB/ΣANHIHL). Thus, low SHI values are indicators of the hydrophilic protein surfaces while high SHI values indicate more hydrophobic protein surfaces. Applying our method to the PDB containing only protein chains we could test Argos? (and ours) hypothesis. We found that 96.7% of oligomeric proteins in PDB have their SHI value in isolation higher (more hydrophobic) than in complex. This data suggests that protein association (for the data mart we examined) is effectively driven by hydrophobic effect where more hydrophobic portions at surface are buried upon complexes formation. In addition, another hypothesis has been proposed: monomer SHI values should be lower (more hydrophilic) than the SHI values of complex subunits alone. We hypothesized that, if oligomerization is driven by hydrophobic patches at surface, the establishment of monomers as "monomers? during evolution is related to the minimization of such patches on their surfaces. Our corresponding datamart shows that on average the SHI value for monomeric proteins with structure deciphered by X ray, is 0.28, against 0.37 for complex subunits alone. These results are important to help understand fully about protein complexes formation and consolidation of oligomers during evolution. We also believe that some other, yet to be defined features, can be deduced through SHI analysis, reinforcing how useful this index is to protein studies.  aBioinformatics  aProteína  aBioinformática  aHidrofobicidade  aÍndice de hidrofobicidade superficial (SHI)  aMecanismos de associação entre proteínas  aProtein1 aMORAES, F. R. de1 aSALIM, J. A.1 aMAZONI, I.1 aMANCINI, A.1 aJARDINE, J. G.1 aNESHICH, G.