NAPS: Network Analysis of Protein Structures

Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue–residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the sequence. NAPS provides users selection of node(s) and its neighbourhood based on centrality measures, physicochemical properties of amino acids or cluster of well-connected residues (k-cliques) for further analysis. Visual analysis of interacting domains and protein chains, and shortest path lengths between pair of residues are additional features that aid in functional analysis. NAPS support various analyses and visualization views for identifying functional residues, provide insight into mechanisms of protein folding, domain-domain and protein–protein interactions for understanding communication within and between proteins. URL:http://bioinf.iiit.ac.in/NAPS/.

[1]  Matteo Tiberti,et al.  xPyder: A PyMOL Plugin To Analyze Coupled Residues and Their Networks in Protein Structures , 2012, J. Chem. Inf. Model..

[2]  Saraswathi Vishveshwara,et al.  GraProStr - Graphs of Protein Structures: A Tool for Constructing the Graphs and Generating Graph Parameters for Protein Structures , 2011 .

[3]  Gergely Fördös,et al.  SeqX: a tool to detect, analyze and visualize residue co-locations in protein and nucleic acid structures , 2005, BMC Bioinformatics.

[4]  B. Chakrabarty,et al.  Analysis of graph centrality measures for identifying Ankyrin repeats , 2012, 2012 World Congress on Information and Communication Technologies.

[5]  R. Nussinov,et al.  Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non‐enzyme families , 2006, Protein science : a publication of the Protein Society.

[6]  Daniele Santoni,et al.  Proteins as Sponges: A Statistical Journey along Protein Structure Organization Principles , 2012, J. Chem. Inf. Model..

[7]  Hari Krishna Yalamanchili,et al.  Graph Spectral Approach for Identifying Protein Domains , 2009, BICoB.

[8]  Kei-Hoi Cheung,et al.  A graph theoretic approach to utilizing protein structure to identify non-random somatic mutations , 2013, BMC Bioinformatics.

[9]  Somdatta Sinha,et al.  Analysis of protein folds using protein contact networks , 2008 .

[10]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

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

[12]  Ernesto Estrada.  Universality in protein residue networks. , 2010, Biophysical journal.

[13]  Janusz M. Bujnicki,et al.  PROTMAP2D: visualization, comparison and analysis of 2D maps of protein structure , 2007, Bioinform..

[14]  Victoria A. Higman,et al.  Uncovering network systems within protein structures. , 2003, Journal of molecular biology.

[15]  P Fariselli,et al.  The effect of backbone on the small-world properties of protein contact maps , 2008, Physical biology.

[16]  Saraswathi Vishveshwara,et al.  Identification of domains and domain interface residues in multidomain proteins from graph spectral method , 2005, Proteins.

[17]  S. Kundu,et al.  Hydrophobic, hydrophilic, and charged amino acid networks within protein. , 2006, Biophysical journal.

[18]  Philip E. Bourne,et al.  Con-Struct Map: a comparative contact map analysis tool , 2007, Bioinform..

[19]  Michael Lappe,et al.  Optimal contact definition for reconstruction of Contact Maps , 2010, BMC Bioinformatics.

[20]  Ying Xu,et al.  Protein domain decomposition using a graph-theoretic approach , 2000, Bioinform..

[21]  Silvio C. E. Tosatto,et al.  RING: networking interacting residues, evolutionary information and energetics in protein structures , 2011, Bioinform..

[22]  Sergey Nepomnyachiy,et al.  CyToStruct: Augmenting the Network Visualization of Cytoscape with the Power of Molecular Viewers. , 2015, Structure.

[23]  Joseph L Greenstein,et al.  The role of stochastic and modal gating of cardiac L-type Ca2+ channels on early after-depolarizations. , 2005, Biophysical journal.

[24]  Bairong Shen,et al.  The construction of an amino acid network for understanding protein structure and function , 2014, Amino Acids.

[25]  Saraswathi Vishveshwara,et al.  Understanding protein structure from a percolation perspective. , 2009, Biophysical journal.

[26]  Aric Hagberg,et al.  Exploring Network Structure, Dynamics, and Function using NetworkX , 2008, Proceedings of the Python in Science Conference.

[27]  S. Vishveshwara,et al.  Identification of side-chain clusters in protein structures by a graph spectral method. , 1999, Journal of molecular biology.

[28]  Csaba Böde,et al.  Network analysis of protein dynamics , 2007, FEBS letters.

[29]  Dániel Kozma,et al.  CMWeb: an interactive on-line tool for analysing residue–residue contacts and contact prediction methods , 2012, Nucleic Acids Res..

[30]  Gennady M Verkhivker,et al.  Molecular Dynamics Simulations and Structural Network Analysis of c-Abl and c-Src Kinase Core Proteins: Capturing Allosteric Mechanisms and Communication Pathways from Residue Centrality , 2015, J. Chem. Inf. Model..

[31]  Md. Aftabuddin,et al.  AMINONET-A TOOL TO CONSTRUCT AND VISUALIZE AMINO ACID NETWORKS, AND TO CALCULATE TOPOLOGICAL PARAMETERS , 2010 .

[32]  Ganesh Bagler,et al.  Assortative mixing in Protein Contact Networks and protein folding kinetics , 2007, Bioinform..

[33]  N. Alves,et al.  Inferring topological features of proteins from amino acid residue networks , 2006, physics/0601128.

[34]  Nita Parekh,et al.  Identifying tandem Ankyrin repeats in protein structures , 2014, BMC Bioinformatics.

[35]  Soumen Roy,et al.  Modeling proteins as residue interaction networks. , 2015, Protein and peptide letters.

[36]  L. Greene.  Protein structure networks. , 2012, Briefings in functional genomics.

[37]  S Vishveshwara,et al.  Backbone cluster identification in proteins by a graph theoretical method. , 2000, Biophysical chemistry.

[38]  A. Giuliani,et al.  Protein contact networks: an emerging paradigm in chemistry. , 2013, Chemical reviews.

[39]  Saraswathi Vishveshwara,et al.  PROTEIN STRUCTURE: INSIGHTS FROM GRAPH THEORY , 2002 .

[40]  Saraswathi Vishveshwara,et al.  Insights into Protein–DNA Interactions through Structure Network Analysis , 2008, PLoS Comput. Biol..

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

[42]  Gábor Csárdi,et al.  The igraph software package for complex network research , 2006 .

[43]  S. Vishveshwara,et al.  Variations in clique and community patterns in protein structures during allosteric communication: investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes. , 2008, Biochemistry.

[44]  Gennady Verkhivker,et al.  Computational Modeling of Allosteric Regulation in the Hsp90 Chaperones: A Statistical Ensemble Analysis of Protein Structure Networks and Allosteric Communications , 2014, PLoS Comput. Biol..

[45]  Nita Parekh,et al.  PRIGSA: Protein repeat identification by graph spectral analysis , 2014, J. Bioinform. Comput. Biol..

[46]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[47]  J. Sussman,et al.  JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia , 2013 .

[48]  R. Nussinov,et al.  Residues crucial for maintaining short paths in network communication mediate signaling in proteins , 2006, Molecular systems biology.

[49]  A. Atilgan,et al.  Screened nonbonded interactions in native proteins manipulate optimal paths for robust residue communication. , 2006, Biophysical journal.

[50]  Neil R. Taylor,et al.  Small world network strategies for studying protein structures and binding , 2013, Computational and structural biotechnology journal.

[51]  Michael P. Cusack,et al.  Efficient Identification of Critical Residues Based Only on Protein Structure by Network Analysis , 2007, PloS one.

[52]  S. Vishveshwara,et al.  A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis , 2007, Proceedings of the National Academy of Sciences.

[53]  A. Atilgan,et al.  Small-world communication of residues and significance for protein dynamics. , 2003, Biophysical journal.

[54]  Saraswathi Vishveshwara,et al.  Correlation of the Side-Chain Hubs with the Functional Residues in DNA Binding Protein Structures , 2006, J. Chem. Inf. Model..

[55]  S. Vishveshwara,et al.  Intra and inter-molecular communications through protein structure network. , 2009, Current protein & peptide science.

[56]  S. Vishveshwara,et al.  A network representation of protein structures: implications for protein stability. , 2005, Biophysical journal.

[57]  Michael Lappe,et al.  CMView: Interactive contact map visualization and analysis , 2011, Bioinform..

[58]  Ganesh Bagler,et al.  Network properties of protein structures , 2004, q-bio/0408009.

[59]  Adam Godzik,et al.  ConSole: using modularity of Contact maps to locate Solenoid domains in protein structures , 2014, BMC Bioinformatics.

[60]  Nadezhda T. Doncheva,et al.  Analyzing and visualizing residue networks of protein structures. , 2011, Trends in biochemical sciences.

[61]  Matteo Tiberti,et al.  PyInteraph: A Framework for the Analysis of Interaction Networks in Structural Ensembles of Proteins , 2014, J. Chem. Inf. Model..

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