Advertisement

Correlation Between Allosteric and Orthosteric Sites

  • Weilin Zhang
  • Juan Xie
  • Luhua LaiEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1163)

Abstract

Correlation between an allosteric site and its orthosteric site refers to the phenomenon that perturbations like ligand binding, mutation, or posttranslational modifications at the allosteric site leverage variation in the orthosteric site. Understanding this kind of correlation not only helps to disclose how information is transmitted in allosteric regulation but also provides clues for allosteric drug discovery. This chapter starts with an overview of correlation studies on allosteric and orthosteric sites and then introduces recent progress in evolutionary and simulation-based dynamic studies. Discussions and perspectives on future directions are also given.

Keywords

Correlation Evolutionary analysis Statistical coupling analysis Elastic network model Molecular dynamics Two state Go̅ model Rigid-body simulation Community analysis Mutual information 

References

  1. 1.
    Amor BRC, Schaub MT, Yaliraki SN, Barahona M (2016) Prediction of allosteric sites and mediating interactions through bond-to-bond propensities. Nat Commun 7:12477–12477PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Atilgan C, Okan OB, Atilgan AR (2012) Network-based models as tools hinting at nonevident protein functionality. Ann Rev Biophys 41(1):205–225CrossRefGoogle Scholar
  3. 3.
    Bahar I, Lezon TR, Yang L-W, Eyal E (2010) Global dynamics of proteins: bridging between structure and function. Ann Rev Biophys 39(1):23–42CrossRefGoogle Scholar
  4. 4.
    David P, Orna R, Kimberly AR (2017) An evolution-based strategy for engineering allosteric regulation. Phys Biol 14(2):025002CrossRefGoogle Scholar
  5. 5.
    Gasper PM, Fuglestad B, Komives EA, Markwick PRL, McCammon JA (2012) Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities. Proc Natl Acad Sci U S A 109(52):21216–21222PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Gunasekaran K, Ma B, Nussinov R (2004) Is allostery an intrinsic property of all dynamic proteins? Proteins 57(3):433–443PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Guo J, Zhou H-X (2016) Protein allostery and conformational dynamics. Chem Soc Rev 116(11):6503–6515CrossRefGoogle Scholar
  8. 8.
    Halabi N, Rivoire O, Leibler S, Ranganathan R (2009) Protein sectors: evolutionary units of three-dimensional structure. Cell 138(4):774–786PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Hilser VJ, Wrabl JO, Motlagh HN (2012) Structural and energetic basis of allostery. Ann Rev Biophys 41(1):585–609CrossRefGoogle Scholar
  10. 10.
    Kalescky R, Liu J, Tao P (2015) Identifying key residues for protein allostery through rigid residue scan. Indian J Chem A 119(9):1689–1700Google Scholar
  11. 11.
    Kalescky R, Zhou H, Liu J, Tao P (2016) Rigid residue scan simulations systematically reveal residue entropic roles in protein allostery. Plos Comput Biol 12(4):e1004893PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Katkar HH, Davtyan A, Durumeric AEP, Hocky GM, Schramm AC, De La Cruz EM, Voth GA (2018) Insights into the cooperative nature of ATP hydrolysis in actin filaments. Biophys J 115(8):1589–1602PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Keul ND, Oruganty K, Schaper Bergman ET, Beattie NR, McDonald WE, Kadirvelraj R, Gross ML, Phillips RS, Harvey SC, Wood ZA (2018) The entropic force generated by intrinsically disordered segments tunes protein function. Nature 563(7732):584–588PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Kobus M, Nguyen PH, Stock G (2011) Coherent vibrational energy transfer along a peptide helix. J Chem Phys 134(12):124518PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kornev AP (2018) Self-organization, entropy and allostery. Biochem Soc T 46(3):587–597CrossRefGoogle Scholar
  16. 16.
    Kornev AP, Taylor SS (2015) Dynamics-driven allostery in protein kinases. Trends Biochem Sci 40(11):628–647PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Kumawat A, Chakrabarty S (2017) Hidden electrostatic basis of dynamic allostery in a PDZ domain. Proc Natl Acad Sci U S A 114(29):E5825–E5834PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Kundu S, Melton JS, Sorensen DC, Phillips GN (2002) Dynamics of proteins in crystals: comparison of experiment with simple models. Biophys J 83(2):723–732PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    La Sala G, Decherchi S, De Vivo M, Rocchia W (2017) Allosteric communication networks in proteins revealed through pocket crosstalk analysis. ACS Cent Sci 3(9):949–960PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Lee J, Natarajan M, Nashine VC, Socolich M, Vo T, Russ WP, Benkovic SJ, Ranganathan R (2008) Surface sites for engineering allosteric control in proteins. Science 322(5900):438–442PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    LeVine MV, Weinstein H (2014) NbIT – a new information theory-based analysis of allosteric mechanisms reveals residues that underlie function in the leucine transporter LeuT. Plos Comput Biol 10(5):e1003603PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Lezon TR, Bahar I (2010) Using entropy maximization to understand the determinants of structural dynamics beyond native contact topology. Plos Comput Biol 6(6):e1000816PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Lockless SW, Ranganathan R (1999) Evolutionarily conserved pathways of energetic connectivity in protein families. Science 286(5438):295–299PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Lu S, Li S, Zhang J (2014) Harnessing allostery: a novel approach to drug discovery. Med Res Rev 34(6):1242–1285PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Ma X, Qi Y, Lai L (2015) Allosteric sites can be identified based on the residue–residue interaction energy difference. Proteins 83(8):1375–1384PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Ma X, Meng H, Lai L (2016) Motions of allosteric and orthosteric ligand-binding sites in proteins are highly correlated. J Chem Inf Model 56(9):1725–1733PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Marks DS, Hopf TA, Sander C (2012) Protein structure prediction from sequence variation. Nat Biotechnol 30:1072PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    McClendon CL, Friedland G, Mobley DL, Amirkhani H, Jacobson MP (2009) Quantifying correlations between allosteric sites in thermodynamic ensembles. J Chem Theory Comput 5(9):2486–2502PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    McClendon CL, Hua L, Barreiro G, Jacobson MP (2012) Comparing conformational ensembles using the Kullback–Leibler divergence expansion. J Chem Theory Comput 8(6):2115–2126PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Meng H, Liu Y, Lai L (2015) Diverse ways of perturbing the human arachidonic acid metabolic network to control inflammation. Acc Chem Res 48(8):2242–2250PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Meng H, McClendon CL, Dai Z, Li K, Zhang X, He S, Shang E, Liu Y, Lai L (2016) Discovery of novel 15-lipoxygenase activators to shift the human arachidonic acid metabolic network toward inflammation resolution. Eur J Med Chem 59(9):4202–4209CrossRefGoogle Scholar
  32. 32.
    Meng H, Dai Z, Zhang W, Liu Y, Lai L (2018) Molecular mechanism of 15-lipoxygenase allosteric activation and inhibition. Phys Chem Chem Phys 20(21):14785–14795PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Miao Y, Nichols SE, Gasper PM, Metzger VT, McCammon JA (2013) Activation and dynamic network of the M2 muscarinic receptor. Proc Natl Acad Sci U S A 110(27):10982–10987PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Miao Y, Feher VA, McCammon JA (2015) Gaussian accelerated molecular dynamics: unconstrained enhanced sampling and free energy calculation. J Chem Theory Comput 11(8):3584–3595PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Mitternacht S, Berezovsky IN (2011) Binding leverage as a molecular basis for allosteric regulation. Plos Comput Biol 7(9):e1002148PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Nguyen PH, Derreumaux P, Stock G (2009) Energy flow and long-range correlations in guanine-binding riboswitch: a nonequilibrium molecular dynamics study. Indian J Chem A 113(27):9340–9347Google Scholar
  37. 37.
    Nussinov R, Tsai C-J (2013) Allostery in disease and in drug discovery. Cell 153(2):293–305PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Nussinov R, Tsai C-J, Liu J (2014) Principles of allosteric interactions in cell signaling. J Am Chem Soc 136(51):17692–17701PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Okazaki K-i, Koga N, Takada S, Onuchic JN, Wolynes PG (2006) Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations. Proc Natl Acad Sci U S A 103(32):11844–11849PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ota N, Agard DA (2005) Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusion. Am J Respir Cell Mol 351(2):345–354Google Scholar
  41. 41.
    Panjkovich A, Daura X (2012) Exploiting protein flexibility to predict the location of allosteric sites. BMC Bioinformatics 13(1):273PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Panjkovich A, Daura X (2014) PARS: a web server for the prediction of Protein Allosteric and Regulatory Sites. Bioinformatics 30(9):1314–1315PubMedCrossRefGoogle Scholar
  43. 43.
    Pei J, Yin N, Ma X, Lai L (2014) Systems biology brings new dimensions for structure-based drug design. J Am Chem Soc 136(33):11556–11565PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Petrone P, Pande VS (2006) Can conformational change be described by only a few normal modes? Biophys J 90(5):1583–1593PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Pierce LCT, Salomon-Ferrer R, de Oliveira CAF, McCammon JA, Walker RC (2012) Routine access to millisecond time scale events with accelerated molecular dynamics. J Chem Theory Comput 8(9):2997–3002PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Pincus D, Pandey JP, Feder ZA, Creixell P, Resnekov O, Reynolds KA (2018) Engineering allosteric regulation in protein kinases. Sci Signal 11(555).  https://doi.org/10.1126/scisignal.aar3250PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Qi Y, Wang Q, Tang B, Lai L (2012) Identifying allosteric binding sites in proteins with a two-state go̅ model for novel allosteric effector discovery. J Chem Theory Comput 8(8):2962–2971PubMedCrossRefGoogle Scholar
  48. 48.
    Reynolds Kimberly A, McLaughlin Richard N, Ranganathan R (2011) Hot spots for allosteric regulation on protein surfaces. Cell 147(7):1564–1575PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Rivoire O, Reynolds KA, Ranganathan R (2016) Evolution-based functional decomposition of proteins. Plos Comput Biol 12(6):e1004817PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Salinas VH, Ranganathan R (2018) Coevolution-based inference of amino acid interactions underlying protein function. eLife 7:e34300PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Sen TZ, Feng Y, Garcia JV, Kloczkowski A, Jernigan RL (2006) The extent of cooperativity of protein motions observed with elastic network models is similar for atomic and coarser-grained models. J Chem Theory Comput 2(3):696–704PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    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):6620–6625PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Sharp K, Skinner JJ (2006) Pump-probe molecular dynamics as a tool for studying protein motion and long range coupling. Proteins 65(2):347–361PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Su JG, Qi LS, Li CH, Zhu YY, Du HJ, Hou YX, Hao R, Wang JH (2014) Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method. Phys Rev E 90(2):022719CrossRefGoogle Scholar
  55. 55.
    Van Wart AT, Durrant J, Votapka L, Amaro RE (2014) Weighted implementation of suboptimal paths (WISP): an optimized algorithm and tool for dynamical network analysis. J Chem Theory Comput 10(2):511–517PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Wang Q, Qi Y, Yin N, Lai L (2014) Discovery of novel allosteric effectors based on the predicted allosteric sites for Escherichia coli D-3-phosphoglycerate dehydrogenase. PLOS One 9(4):e94829PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Wang Q, Liberti MV, Liu P, Deng X, Liu Y, Locasale JW, Lai L (2017) Rational design of selective allosteric inhibitors of PHGDH and serine synthesis with anti-tumor activity. Cell Chem Biol 24(1):55–65PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Xu Y, Wang S, Hu Q, Gao S, Ma X, Zhang W, Shen Y, Chen F, Lai L, Pei J (2018) CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction. Nucleic Acids Res 46(W1):W374–W379PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Yang L-W, Eyal E, Chennubhotla C, Jee J, Gronenborn AM, Bahar I (2007) Insights into equilibrium dynamics of proteins from comparison of NMR and X-ray data with computational predictions. Structure 15(6):741–749PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Yu M, Ma X, Cao H, Chong B, Lai L, Liu Z (2018) Singular value decomposition for the correlation of atomic fluctuations with arbitrary angle. Proteins 86(10):1075–1087PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Yuan Y, Pei J, Lai L (2013) Binding site detection and druggability prediction of protein targets for structure-based drug design. Curr Pharm Design 19(12):2326–2333CrossRefGoogle Scholar
  62. 62.
    Zhou H, Dong Z, Tao P (2018) Recognition of protein allosteric states and residues: machine learning approaches. J Comput Chem 39(20):1481–1490PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Li C, Deng X, Zhang W, Xie X, Conrad M, Liu Y, Angeli JPF, Lai L (2018) Novel allosteric activators for ferroptosis regulator glutathione peroxidase 4. J Med Chem 62(1):266–275PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.Center for Quantitative Biology, AAISPeking UniversityBeijingChina

Personalised recommendations