HotRegion: a database of predicted hot spot clusters

Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided. HotRegion is accessible at http://prism.ccbb.ku.edu.tr/hotregion.

[1]  C. Kleanthous,et al.  Immunity proteins: enzyme inhibitors that avoid the active site. , 2001, Trends in biochemical sciences.

[2]  Ozlem Keskin,et al.  Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy , 2009, Bioinform..

[3]  Juliette Martin.  Beauty Is in the Eye of the Beholder: Proteins Can Recognize Binding Sites of Homologous Proteins in More than One Way , 2010, PLoS Comput. Biol..

[4]  Ozlem Keskin,et al.  HotPoint: hot spot prediction server for protein interfaces , 2010, Nucleic Acids Res..

[5]  Anna R Panchenko,et al.  Exploring functional roles of multibinding protein interfaces , 2009, Protein science : a publication of the Protein Society.

[6]  Ozlem Keskin,et al.  CCRXP: exploring clusters of conserved residues in protein structures , 2010, Nucleic Acids Res..

[7]  Ozlem Keskin,et al.  HotSprint: database of computational hot spots in protein interfaces , 2007, Nucleic Acids Res..

[8]  D. Baker,et al.  A simple physical model for binding energy hot spots in protein–protein complexes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

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

[10]  Angel Herráez,et al.  Biomolecules in the computer: Jmol to the rescue , 2006, Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology.

[11]  H. Wolfson,et al.  Protein-Protein Interactions: Coupling of Structurally Conserved Residues and of Hot Spots across Interfaces. Implications for Docking , 2004 .

[12]  Ruth Nussinov,et al.  Energetic determinants of protein binding specificity: Insights into protein interaction networks , 2009, Proteomics.

[13]  P. Chakrabarti,et al.  Conservation and relative importance of residues across protein-protein interfaces , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Janin,et al.  Dissecting protein–protein recognition sites , 2002, Proteins.

[15]  Tanja Kortemme,et al.  Design of Multi-Specificity in Protein Interfaces , 2007, PLoS Comput. Biol..

[16]  D. F. Waugh,et al.  Protein-protein interactions. , 1954, Advances in protein chemistry.

[17]  Ozlem Keskin,et al.  Similar binding sites and different partners: implications to shared proteins in cellular pathways. , 2007, Structure.

[18]  Ruth Nussinov,et al.  MultiBind and MAPPIS: webservers for multiple alignment of protein 3D-binding sites and their interactions , 2008, Nucleic Acids Res..

[19]  N. Ben-Tal,et al.  ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic information. , 2001, Journal of molecular biology.

[20]  O. Dym,et al.  The modular architecture of protein-protein binding interfaces. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. I. Izpisúa Belmonte,et al.  Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes , 2014, Protein & Cell.

[22]  D. Baker,et al.  The structural and energetic basis for high selectivity in a high-affinity protein-protein interaction , 2010, Proceedings of the National Academy of Sciences.

[23]  T. Clackson,et al.  A hot spot of binding energy in a hormone-receptor interface , 1995, Science.

[24]  David M Kranz,et al.  Long-range cooperative binding effects in a T cell receptor variable domain. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Wolfson,et al.  A new, structurally nonredundant, diverse data set of protein–protein interfaces and its implications , 2004, Protein science : a publication of the Protein Society.

[26]  Ozlem Keskin,et al.  Analysis of Hot Region Organization in Hub Proteins , 2010, Annals of Biomedical Engineering.

[27]  A. Bogan,et al.  Anatomy of hot spots in protein interfaces. , 1998, Journal of molecular biology.

[28]  H. Wolfson,et al.  Spatial chemical conservation of hot spot interactions in protein-protein complexes , 2007, BMC Biology.

[29]  J. Wells,et al.  Systematic mutational analyses of protein-protein interfaces. , 1991, Methods in enzymology.

[30]  Philip M. Kim,et al.  Relating Three-Dimensional Structures to Protein Networks Provides Evolutionary Insights , 2006, Science.

[31]  Mainak Guharoy,et al.  Empirical estimation of the energetic contribution of individual interface residues in structures of protein–protein complexes , 2009, J. Comput. Aided Mol. Des..

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

[33]  R. Nussinov,et al.  Hot regions in protein--protein interactions: the organization and contribution of structurally conserved hot spot residues. , 2005, Journal of molecular biology.

[34]  Ozlem Keskin,et al.  Architectures and functional coverage of protein-protein interfaces. , 2008, Journal of molecular biology.

[35]  Julie C. Mitchell,et al.  KFC2: A knowledge‐based hot spot prediction method based on interface solvation, atomic density, and plasticity features , 2011, Proteins.

[36]  Christopher J. R. Illingworth,et al.  Connectivity and binding‐site recognition: Applications relevant to drug design , 2010, J. Comput. Chem..

[37]  H. Wolfson,et al.  A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique. , 1996, Journal of molecular biology.

[38]  V. Hilser,et al.  Functional residues serve a dominant role in mediating the cooperativity of the protein ensemble , 2007, Proceedings of the National Academy of Sciences.