Binding similarity network of ligand

The protein and ligand interaction takes an important part in protein function. Both ligand and its binding site are essential components for understanding how the protein–ligand complex functions. Until now, there have been many studies about protein function and evolution, but they usually lacked ligand information. Accordingly, in this study, we tried to answer the following questions: how much ligand and binding site are associated with protein function, and how ligands themselves are related to each other in terms of binding site. To answer the questions, we presented binding similarity network of ligand. Through the network analysis, we attempted to reveal systematic relationship between the ligand and binding site. The results showed that ligand binding site and function were closely related (conservation ratio, 81%). We also showed conservative tendency of function in line with ligand structure similarity with some exceptional cases. In addition, the binding similarity network of ligand revealed scale‐free property to some degree like other biological networks. Since most nodes formed highly connected cluster, a clustering coefficient was very high compared with random. All the highly connected ligands (hubs) were involved in various functions forming large cluster and tended to act as a bridge between modular clusters in the network. Proteins 2008. © 2007 Wiley‐Liss, Inc.

[1]  C. Bron,et al.  Algorithm 457: finding all cliques of an undirected graph , 1973 .

[2]  Coenraad Bron,et al.  Finding all cliques of an undirected graph , 1973 .

[3]  Robert D Clark,et al.  Neighborhood behavior: a useful concept for validation of "molecular diversity" descriptors. , 1996, Journal of medicinal chemistry.

[4]  C. Craik,et al.  Engineering enzyme specificity. , 1998, Current opinion in chemical biology.

[5]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[6]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

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

[8]  B. Schwikowski,et al.  A network of protein–protein interactions in yeast , 2000, Nature Biotechnology.

[9]  T. Ito,et al.  Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Barabasi,et al.  Lethality and centrality in protein networks , 2001, Nature.

[11]  Jong H. Park,et al.  Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast. , 2001, Journal of molecular biology.

[12]  Michael J E Sternberg,et al.  Evolution of enzymes in metabolism: a network perspective. , 2002, Journal of molecular biology.

[13]  Robert P Sheridan,et al.  Why do we need so many chemical similarity search methods? , 2002, Drug discovery today.

[14]  Susumu Goto,et al.  LIGAND: database of chemical compounds and reactions in biological pathways , 2002, Nucleic Acids Res..

[15]  G. Klebe,et al.  A new method to detect related function among proteins independent of sequence and fold homology. , 2002, Journal of molecular biology.

[16]  B. Snel,et al.  Comparative assessment of large-scale data sets of protein–protein interactions , 2002, Nature.

[17]  Jie Liang,et al.  Inferring functional relationships of proteins from local sequence and spatial surface patterns. , 2003, Journal of molecular biology.

[18]  K. Kinoshita,et al.  Identification of protein biochemical functions by similarity search using the molecular surface database eF‐site , 2003, Protein science : a publication of the Protein Society.

[19]  P. Bork,et al.  Metabolites: a helping hand for pathway evolution? , 2003, Trends in biochemical sciences.

[20]  S. J. Campbell,et al.  Ligand binding: functional site location, similarity and docking. , 2003, Current opinion in structural biology.

[21]  Alessandro Vespignani,et al.  Global protein function prediction from protein-protein interaction networks , 2003, Nature Biotechnology.

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

[23]  H. Wolfson,et al.  Recognition of Functional Sites in Protein Structures☆ , 2004, Journal of Molecular Biology.

[24]  T. Transue,et al.  X-ray and NMR characterization of covalent complexes of trypsin, borate, and alcohols. , 2004, Biochemistry.

[25]  R. Glen,et al.  Molecular similarity: a key technique in molecular informatics. , 2004, Organic & biomolecular chemistry.

[26]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[27]  Andrew C. R. Martin.  PDBSprotEC: a Web-accessible database linking PDB chains to EC numbers via SwissProt , 2004, Bioinform..

[28]  Gabriele Ausiello,et al.  Functional annotation by identification of local surface similarities: a novel tool for structural genomics , 2005, BMC Bioinformatics.

[29]  Michael G. Lerner,et al.  Binding MOAD (Mother Of All Databases) , 2005, Proteins.

[30]  Stuart L Schreiber,et al.  Small molecules: the missing link in the central dogma , 2005, Nature chemical biology.

[31]  R. Nussinov,et al.  Favorable scaffolds: proteins with different sequence, structure and function may associate in similar ways. , 2005, Protein engineering, design & selection : PEDS.

[32]  John S. Delaney,et al.  Assessing the ability of chemical similarity measures to discriminate between active and inactive compounds , 1996, Molecular Diversity.

[33]  Péter Csermely,et al.  The efficiency of multi-target drugs: the network approach might help drug design. , 2004, Trends in pharmacological sciences.

[34]  S. Frantz.  Drug discovery: Playing dirty , 2005, Nature.

[35]  John P. Overington,et al.  Can we rationally design promiscuous drugs? , 2006, Current opinion in structural biology.

[36]  Ziding Zhang,et al.  Similarity networks of protein binding sites , 2005, Proteins.

[37]  Pasch,et al.  References and Notes Supporting Online Material Evolution of Hormone-receptor Complexity by Molecular Exploitation , 2022 .

[38]  Keunwan Park,et al.  A method to detect important residues using protein binding site comparison. , 2006, Genome informatics. International Conference on Genome Informatics.

[39]  Ruth Nussinov,et al.  Ligand Binding and Circular Permutation Modify Residue Interaction Network in DHFR , 2007, PLoS Comput. Biol..

[40]  Michael J. Keiser,et al.  Relating protein pharmacology by ligand chemistry , 2007, Nature Biotechnology.