Efficient Identification of Critical Residues Based Only on Protein Structure by Network Analysis

Despite the increasing number of published protein structures, and the fact that each protein's function relies on its three-dimensional structure, there is limited access to automatic programs used for the identification of critical residues from the protein structure, compared with those based on protein sequence. Here we present a new algorithm based on network analysis applied exclusively on protein structures to identify critical residues. Our results show that this method identifies critical residues for protein function with high reliability and improves automatic sequence-based approaches and previous network-based approaches. The reliability of the method depends on the conformational diversity screened for the protein of interest. We have designed a web site to give access to this software at http://bis.ifc.unam.mx/jamming/. In summary, a new method is presented that relates critical residues for protein function with the most traversed residues in networks derived from protein structures. A unique feature of the method is the inclusion of the conformational diversity of proteins in the prediction, thus reproducing a basic feature of the structure/function relationship of proteins.

[1]  D. Eisenberg,et al.  Protein function in the post-genomic era , 2000, Nature.

[2]  M Karplus,et al.  Small-world view of the amino acids that play a key role in protein folding. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[3]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[4]  Shimon Even,et al.  Graph Algorithms , 1979 .

[5]  Knut Reinert,et al.  Calibration of mass spectrometric peptide mass fingerprint data without specific external or internal calibrants , 2005, BMC Bioinformatics.

[6]  Annabel E. Todd,et al.  From structure to function: Approaches and limitations , 2000, Nature Structural Biology.

[7]  Michael Philippsen,et al.  JavaParty – transparent remote objects in Java , 1997 .

[8]  Jie Liang,et al.  CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues , 2006, Nucleic Acids Res..

[9]  Peter S. Shenkin,et al.  Amino Acid Sequence Determinants of β-Lactamase Structure and Activity , 1996 .

[10]  A. del Sol,et al.  Small‐world network approach to identify key residues in protein–protein interaction , 2004, Proteins.

[11]  C. Sander,et al.  A database of protein structure families with common folding motifs , 1992, Protein science : a publication of the Protein Society.

[12]  S. Bouvier,et al.  Systematic mutation of bacteriophage T4 lysozyme. , 1991, Journal of molecular biology.

[13]  S. Bouvier,et al.  Functional significance of conserved amino acid residues , 1992, Proteins.

[14]  A. Elcock.  Prediction of functionally important residues based solely on the computed energetics of protein structure. , 2001, Journal of molecular biology.

[15]  Gil Amitai,et al.  Network analysis of protein structures identifies functional residues. , 2004, Journal of molecular biology.

[16]  Gail J. Bartlett,et al.  Effective function annotation through catalytic residue conservation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Mark Gerstein,et al.  Structural proteomics of an archaeon , 2000, Nature Structural Biology.

[18]  M. Sternberg,et al.  Automated prediction of protein function and detection of functional sites from structure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Mark Allen Weiss,et al.  Data structures & algorithm analysis in Java , 1999 .

[20]  D. Eisenberg,et al.  Inference of protein function from protein structure. , 2005, Structure.

[21]  A. Valencia,et al.  Automatic methods for predicting functionally important residues. , 2003, Journal of molecular biology.

[22]  A. Valencia,et al.  Practical limits of function prediction , 2000, Proteins.

[23]  Marianne Manchester,et al.  Complete mutagenesis of the HIV-1 protease , 1989, Nature.

[24]  S. Benkovic,et al.  A Perspective on Enzyme Catalysis , 2003, Science.

[25]  Gabriel del Rio,et al.  Improved prediction of critical residues for protein function based on network and phylogenetic analyses , 2005, BMC Bioinformatics.

[26]  Karsten Suhre,et al.  ElNémo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement , 2004, Nucleic Acids Res..

[27]  Tal Pupko,et al.  Structural Genomics , 2005 .

[28]  D. Ringe,et al.  Locating and characterizing binding sites on proteins , 1996, Nature Biotechnology.

[29]  Lewis E. Kay,et al.  New Tools Provide New Insights in NMR Studies of Protein Dynamics , 2006, Science.

[30]  Michael Philippsen,et al.  JavaParty - Transparent Remote Objects in Java , 1997, Concurr. Pract. Exp..