6 – Use of the “fuzzy oil drop” model to identify the complexation area in protein homodimers

: The aim of this chapter is to demonstrate how an analysis of the hydrophobicity distribution in homodimers can help identify complexation areas in each participating protein. Irregularities in the observed distribution of hydrophobicity, when compared with the expected, well-ordered distribution, may be treated as criteria for recognition of complexation sites. The reliability of this approach is verified using ROC diagrams. The relation between the true positive ratio and the false positive ratio calculated for local hydrophobicity maxima (deficiencies) and minima (excesses) shows that the model matches experimental observations. A case study involving a set of sample proteins is also presented.

[1]  Pinak Chakrabarti,et al.  Macromolecular recognition in the Protein Data Bank , 2006, Acta crystallographica. Section D, Biological crystallography.

[2]  Sandor Vajda,et al.  Modeling of protein interactions in genomes , 2002, Proteins.

[3]  Roger A. Moore,et al.  A structural basis for the mechanism of aspartate‐β‐semialdehyde dehydrogenase from Vibrio cholerae , 2003, Protein science : a publication of the Protein Society.

[4]  G. J. Swaminathan,et al.  The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution* , 2001, The Journal of Biological Chemistry.

[5]  I Roterman,et al.  Two-intermediate model to characterize the structure of fast-folding proteins. , 2011, Journal of theoretical biology.

[6]  Sandor Vajda,et al.  CAPRI: A Critical Assessment of PRedicted Interactions , 2003, Proteins.

[7]  J. Janin.  Assessing predictions of protein–protein interaction: The CAPRI experiment , 2005, Protein science : a publication of the Protein Society.

[8]  Ruth Nussinov,et al.  Combinatorial docking approach for structure prediction of large proteins and multi-molecular assemblies , 2005, Physical biology.

[9]  D. Gallagher,et al.  Structure of the class IV adenylyl cyclase reveals a novel fold. , 2006, Journal of molecular biology.

[10]  C. Landry,et al.  An in Vivo Map of the Yeast Protein Interactome , 2008, Science.

[11]  W. Gärtner,et al.  Crystal structures of two cyanobacterial response regulators in apo- and phosphorylated form reveal a novel dimerization motif of phytochrome-associated response regulators. , 2004, Biophysical journal.

[12]  Joël Janin,et al.  The third CAPRI assessment meeting Toronto, Canada, April 20-21, 2007. , 2007, Structure.

[13]  Tom Fawcett,et al.  An introduction to ROC analysis , 2006, Pattern Recognit. Lett..

[14]  Joël Janin.  Sailing the route from Gaeta, Italy, to CAPRI , 2005, Proteins.

[15]  S. L. Wong,et al.  Towards a proteome-scale map of the human protein–protein interaction network , 2005, Nature.

[16]  Joël Janin,et al.  The targets of CAPRI Rounds 13–19 , 2010, Proteins.

[17]  Joël Janin,et al.  Protein-protein docking tested in blind predictions: the CAPRI experiment. , 2010, Molecular bioSystems.

[18]  S. B. Needleman,et al.  A general method applicable to the search for similarities in the amino acid sequence of two proteins. , 1970, Journal of molecular biology.

[19]  Wei Zu Chen,et al.  A soft docking algorithm for predicting the structure of antibody‐antigen complexes , 2003, Proteins: Structure, Function, and Bioinformatics.

[20]  B. Beatrix,et al.  The Crystal Structure of Archaeal Nascent Polypeptide-associated Complex (NAC) Reveals a Unique Fold and the Presence of a Ubiquitin-associated Domain* , 2005, Journal of Biological Chemistry.

[21]  S Marangoni,et al.  Structural basis for low catalytic activity in Lys49 phospholipases A2--a hypothesis: the crystal structure of piratoxin II complexed to fatty acid. , 2001, Biochemistry.

[22]  Takanori Muto,et al.  Structures of the extracellular regions of the group II/III metabotropic glutamate receptors , 2007, Proceedings of the National Academy of Sciences.

[23]  Joël Janin,et al.  Welcome to CAPRI: A Critical Assessment of PRedicted Interactions , 2002 .

[24]  R. Nussinov,et al.  Protein–protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach , 2005, Physical biology.

[25]  B. Rost,et al.  Analysing six types of protein-protein interfaces. , 2003, Journal of molecular biology.

[26]  Joël Janin,et al.  Genome-wide studies of protein-protein interaction. , 2003, Current opinion in structural biology.