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Community Network Analysis of Allosteric Proteins

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Allostery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2253))

Abstract

Community network analysis (CNA) of correlated protein motions allows modeling of signals propagation in allosteric proteic systems. From standard classical molecular dynamics (MD) simulations, protein motions can be analysed by means of mutual information between pairs of amino acid residues, providing dynamical weighted networks that contains fundamental information of the communication among amino acids. The CNA method has been successfully applied to a variety of allosteric systems including an enzyme, a nuclear receptor and a bacterial adaptive immune system, providing characterization of the allosteric pathways. This method is complementary to network analyses based on different metrics and it is particularly powerful for studying large proteic systems, as it provides a coarse-grained view of the communication flows within large and complex networks.

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References

  1. Fenton AW (2008) Allostery: an illustrated definition for the ‘second secret of life’. Trends Biochem Sci 33(9):420–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Changeux JP (2013) 50 years of allosteric interactions: the twists and turns of the models. Nat Rev Mol Cell Biol 14(12):819–829

    Article  CAS  PubMed  Google Scholar 

  3. Hilser VJ, Wrabl JO, Motlagh HN (2012) Structural and energetic basis of allostery. Annu Rev Biophys 41:585–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tsai CJ, Nussinov R (2014) A unified view of “how allostery works”. PLoS Comput Biol 10(2):e1003394

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Wodak SJ, Paci E, Dokholyan NV, Berezovsky IN, Horovitz A, Li J, Hilser VJ, Bahar I, Karanicolas J, Stock G, Hamm P, Stote RH, Eberhardt J, Chebaro Y, Dejaegere A, Cecchini M, Changeux J-P, Bolhuis PG, Vreede J, Faccioli P, Orioli S, Ravasio R, Yan L, Brito C, Wyart M, Gkeka P, Rivalta I, Palermo G, McCammon JA, Panecka-Hofman J, Wade RC, Di Pizio A, Niv MY, Nussinov R, Tsai C-J, Jang H, Padhorny D, Kozakov D, McLeish T (2019) Allostery in its many disguises: from theory to applications. Structure 27(4):566–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wootten D, Christopoulos A, Sexton PM (2013) Emerging paradigms in gpcr allostery: implications for drug discovery. Nat Rev Drug Discov 12(8):630–644

    Article  CAS  PubMed  Google Scholar 

  7. Taly A, Corringer PJ, Guedin D, Lestage P, Changeux JP (2009) Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov 8(9):733–750

    Article  CAS  PubMed  Google Scholar 

  8. Nussinov R, Tsai CJ (2013) Allostery in disease and in drug discovery. Cell 153(2):293–305

    Article  CAS  PubMed  Google Scholar 

  9. Christopoulos A (2002) Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 1(3):198–210

    Article  CAS  PubMed  Google Scholar 

  10. Gohara DW, Di Cera E (2011) Allostery in trypsin-like proteases suggests new therapeutic strategies. Trends Biotechnol 29(11):577–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Makhlynets OV, Raymond EA, Korendovych IV (2015) Design of allosterically regulated protein catalysts. Biochemistry 54(7):1444–1456

    Article  CAS  PubMed  Google Scholar 

  12. Lisi GP, Manley GA, Hendrickson H, Rivalta I, Batista VS, Loria JP (2016) Dissecting dynamic allosteric pathways using chemically related small-molecule activators. Structure 24(7):1155–1166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Suel GM, Lockless SW, Wall MA, Ranganathan R (2003) Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nat Struct Biol 10(1):59–69

    Article  PubMed  CAS  Google Scholar 

  14. Amaro RE, Sethi A, Myers RS, Davisson VJ, Luthey-Schulten ZA (2007) A network of conserved interactions regulates the allosteric signal in a glutamine amidotransferase. Biochemistry 46(8):2156–2173

    Article  CAS  PubMed  Google Scholar 

  15. Bruschweiler S, Schanda P, Kloiber K, Brutscher B, Kontaxis G, Konrat R, Tollinger M (2009) Direct observation of the dynamic process underlying allosteric signal transmission. J Am Chem Soc 131(8):3063–3068

    Article  CAS  PubMed  Google Scholar 

  16. del Sol A, Tsai CJ, Ma B, Nussinov R (2009) The origin of allosteric functional modulation: multiple pre-existing pathways. Structure 17(8):1042–1050

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Feher VA, Durrant JD, Van Wart AT, Amaro RE (2014) Computational approaches to mapping allosteric pathways. Curr Opin Struct Biol 25:98–103

    Article  CAS  PubMed  Google Scholar 

  18. Martin NE, Malik S, Calimet N, Changeux JP, Cecchini M (2017) Un-gating and allosteric modulation of a pentameric ligand-gated ion channel captured by molecular dynamics. PLoS Comput Biol 13(10):e1005784

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Markwick PR, McCammon JA (2011) Studying functional dynamics in bio-molecules using accelerated molecular dynamics. Phys Chem Chem Phys 13(45):20053–20065

    Article  CAS  PubMed  Google Scholar 

  20. De Vivo M, Masetti M, Bottegoni G, Cavalli A (2016) Role of molecular dynamics and related methods in drug discovery. J Med Chem 59(9):4035–4061

    Article  PubMed  CAS  Google Scholar 

  21. Di Paola L, Giuliani A (2015) Protein contact network topology: a natural language for allostery. Curr Opin Struct Biol 31:43–48

    Article  PubMed  CAS  Google Scholar 

  22. Di Paola L, De Ruvo M, Paci P, Santoni D, Giuliani A (2013) Protein contact networks: an emerging paradigm in chemistry. Chem Rev 113(3):1598–1613

    Article  PubMed  CAS  Google Scholar 

  23. Rivalta I, Sultan MM, Lee NS, Manley GA, Loria JP, Batista VS (2012) Allosteric pathways in imidazole glycerol phosphate synthase. Proc Natl Acad Sci U S A 109(22):E1428–E1436

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ricci CG, Silveira RL, Rivalta I, Batista VS, Skaf MS (2016) Allosteric pathways in the pparγ-rxrα nuclear receptor complex. Sci Rep 6:19940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Palermo G, Ricci CG, Fernando A, Basak R, Jinek M, Rivalta I, Batista VS, McCammon JA (2017) Protospacer adjacent motif-induced allostery activates crispr-cas9. J Am Chem Soc 139(45):16028–16031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Negre CFA, Morzan UN, Hendrickson HP, Pal R, Lisi GP, Loria JP, Rivalta I, Ho J, Batista VS (2018) Eigenvector centrality for characterization of protein allosteric pathways. Proc Natl Acad Sci U S A 115(52):E12201–E12208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sethi A, Eargle J, Black AA, Luthey-Schulten Z (2009) Dynamical networks in tRNA: protein complexes. Proc Natl Acad Sci U S A 106(16):6620–6625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gasper PM, Fuglestad B, Komives EA, Markwick PR, McCammon JA (2012) Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities. Proc Natl Acad Sci U S A 109(52):21216–21222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Blacklock K, Verkhivker GM (2014) Computational modeling of allosteric regulation in the hsp90 chaperones: a statistical ensemble analysis of protein structure networks and allosteric communications. PLoS Comput Biol 10(6):e1003679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Stolzenberg S, Michino M, LeVine MV, Weinstein H, Shi L (2016) Computational approaches to detect allosteric pathways in transmembrane molecular machines. Biochim Biophys Acta 1858(7 Pt B):1652–1662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wagner JR, Lee CT, Durrant JD, Malmstrom RD, Feher VA, Amaro RE (2016) Emerging computational methods for the rational discovery of allosteric drugs. Chem Rev 116(11):6370–6390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rivalta I, Lisi GP, Snoeberger NS, Manley G, Loria JP, Batista VS (2016) Allosteric communication disrupted by a small molecule binding to the imidazole glycerol phosphate synthase protein-protein interface. Biochemistry 55(47):6484–6494

    Article  CAS  PubMed  Google Scholar 

  33. Chaudhuri BN, Lange SC, Myers RS, Chittur SV, Davisson VJ, Smith JL (2001) Crystal structure of imidazole glycerol phosphate synthase: a tunnel through a (beta/alpha)(8) barrel joins two active sites. Structure 9(10):987–997

    Article  CAS  PubMed  Google Scholar 

  34. Breitbach K, Köhler J, Steinmetz I (2008) Induction of protective immunity against burkholderia pseudomallei using attenuated mutants with defects in the intracellular life cycle. Trans R Soc Trop Med Hyg 102:S89–S94

    Article  PubMed  Google Scholar 

  35. Gomez MJ, Neyfakh AA (2006) Genes involved in intrinsic antibiotic resistance of acinetobacter baylyi. Antimicrob Agents Chemother 50(11):3562–3567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28(1):235–242. http://www.rcsb.org/pdb/

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The amber biomolecular simulation programs. J Comput Chem 26(16):1668–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) Gromacs 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4(3):435–447

    Article  CAS  PubMed  Google Scholar 

  39. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K (2005) Scalable molecular dynamics with namd. J Comput Chem 26(16):1781–1802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. See webpage: https://ambermd.org/tutorials/

  41. See webpage: http://www.Ks.Uiuc.Edu/training/tutorials/namd-index.Html

  42. See webpage: http://www.Gromacs.Org/documentation/tutorials

  43. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25(9):1157–1174

    Article  CAS  PubMed  Google Scholar 

  44. Lange OF, Grubmuller H (2006) Generalized correlation for biomolecular dynamics. Proteins 62(4):1053–1061

    Article  CAS  PubMed  Google Scholar 

  45. Kraskov A, Stogbauer H, Grassberger P (2004) Estimating mutual information. Phys Rev E Stat Nonlinear Soft Matter Phys 69(6 Pt 2):066138

    Article  CAS  Google Scholar 

  46. See webpage: https://parmed.github.io/parmed/html/parmed.html

  47. Floyd RW (1962) Algorithm-97—shortest path. Commun ACM 5(6):345–345

    Article  Google Scholar 

  48. Girvan M, Newman MEJ (2002) Community structure in social and biological networks. Proc Natl Acad Sci U S A 99(12):7821–7826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Newman MEJ, Girvan M (2004) Finding and evaluating community structure in networks. Phys Rev E 69(2):026113

    Article  CAS  Google Scholar 

  50. Lipchock J, Loria JP (2009) Millisecond dynamics in the allosteric enzyme imidazole glycerol phosphate synthase (igps) from thermotoga maritima. J Biomol NMR 45(1–2):73–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lipchock JM, Loria JP (2010) Nanometer propagation of millisecond motions in v-type allostery. Structure 18(12):1596–1607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Myers RS, Jensen JR, Deras IL, Smith JL, Davisson VJ (2003) Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synthase. Biochemistry 42(23):7013–7022

    Article  CAS  PubMed  Google Scholar 

  53. Lisi GP, East KW, Batista VS, Loria JP (2017) Altering the allosteric pathway in igps suppresses millisecond motions and catalytic activity. Proc Natl Acad Sci U S A 114(17):E3414–E3423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gheeraert A, Pacini L, Batista VS, Vuillon L, Lesieur C, Rivalta I (2019) Exploring allosteric pathways of a v-type enzyme with dynamical perturbation networks. J Phys Chem B 123(16):3452–3461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Humphrey W, Dalke A, Schulten K (1996) Vmd: visual molecular dynamics. J Mol Graph Model 14(1):33–38

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Dipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Bologna, Italy

    Ivan Rivalta

  2. Univ Lyon, Ens de Lyon, CNRS, Université Lyon 1, Laboratoire de Chimie UMR 5182, Lyon, France

    Ivan Rivalta

  3. Department of Chemistry, Yale University, New Haven, CT, USA

    Victor S. Batista

  4. Energy Sciences Institute, Yale University, New Haven, CT, USA

    Victor S. Batista

Authors
  1. Ivan Rivalta
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  2. Victor S. Batista
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Corresponding author

Correspondence to Ivan Rivalta .

Editor information

Editors and Affiliations

  1. Unit of Chemical-Physics Fundamentals in Chemical Engineering Department of Engineering, Universitá Campus Bio-Medico di Rome, Rome, Italy

    Luisa Di Paola

  2. Environment and Health Department, Instituto Superiore di Sanità, Rome, Italy

    Alessandro Giuliani

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Rivalta, I., Batista, V.S. (2021). Community Network Analysis of Allosteric Proteins. In: Di Paola, L., Giuliani, A. (eds) Allostery. Methods in Molecular Biology, vol 2253. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1154-8_9

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  • DOI: https://doi.org/10.1007/978-1-0716-1154-8_9

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1153-1

  • Online ISBN: 978-1-0716-1154-8

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