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DNA cleavage by endonuclease I-DmoI: a QM/MM study and comparison with experimental data provide indications on the environmental effects

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Abstract

Here, we present the theoretical–computational modelling of the free energy barrier of the phosphodiester bond cleavage as occurring in the mesophilic variant of endonuclease I-DmoI bound to DNA. Our data, obtained by means of hybrid quantum mechanics/molecular mechanics approach, indicate that the influence of the environment, exerted by the enzyme, the solvent and the DNA, shifts the mechanism towards a more dissociative reaction pathway, compared to the unperturbed reaction. The perturbation of the environment results in an earlier transition state of hydrolysis, i.e. more similar to reagents. By such an approach, we estimate that the enzyme lowers the phosphorus–oxygen bond break free energy barrier of about 7.9 kcal/mol compared to the gas phase, which turns out to be consistent with experimental data. Such an approach points out the importance of an extended and accurate treatment of the environmental effects in the modelling of chemical reactions and confirms the reliability of our procedure in the modelling of important biochemical processes at a limited computational cost.

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References

  1. Schroeder GK, Lad C, Wyman P, Williams NH, Wolfenden R (2006) PNAS 103:4052–4055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yang W (2011) Q Rev Biophys 44:1–93

    Article  CAS  PubMed  Google Scholar 

  3. Prieto J, Epinat JC, Redondo P, Ramos E, Padro D, Cedrone F, Montoya G, Paques F, Blanco FJ (2008) J Biol Chem 283:4364–4374

    Article  CAS  PubMed  Google Scholar 

  4. Dalgaardl JZ, Garrett RA, Belfort M (1994) J Biol Chem 269:28885–28892

    Google Scholar 

  5. Pereira MS, Murta B, Oliveira TC, Manfredi AM, Nome F, Hengge AC, Brandao TA (2016) J Org Chem 81:8663–8672

    Article  CAS  PubMed  Google Scholar 

  6. Wu J, Wang X, Wang Q, Lou Z, Li S, Zhu Y, Qin L, Wei H (2019) Chem Soc Rev 48:1004–1076

    Article  CAS  PubMed  Google Scholar 

  7. Kuah E, Toh S, Yee J, Ma Q, Gao Z (2016) Chem Eur J 22:8404–8430

    Article  CAS  PubMed  Google Scholar 

  8. Salvio R, Cincotti A (2014) RSC Adv 4:28678–28682

    Article  CAS  Google Scholar 

  9. Salvio R, Cacciapaglia R, Mandolini L, Sansone F, Casnati A (2014) RSC Adv 4:34412–34416

    Article  CAS  Google Scholar 

  10. Raynal M, Ballester P, Vidal-Ferran A, van Leeuwen PW (2014) Chem Soc Rev 43:1734–1787

    Article  CAS  PubMed  Google Scholar 

  11. López-Canut V, Roca M, Bertrán J, Moliner V, Tuñón I (2010) J Am Chem Soc 132:6955–6963

    Article  CAS  PubMed  Google Scholar 

  12. Zalatan JG, Herschlag D (2006) J Am Chem Soc 128:1293–1303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kamerlin SC, Sharma PK, Prasad RB, Warshel A (2013) Q Rev Biophys 46:1–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hu CH, Brinck T (1999) J Phys Chem A 103:5379–5386

    Article  CAS  Google Scholar 

  15. Pereira ES, Da Silva JC, Brandao TA, Rocha WR (2016) Phys Chem Chem Phys 18:18255–18267

    Article  CAS  PubMed  Google Scholar 

  16. Prasad BR, Plotnikov NV, Warshel A (2013) J Phys Chem B 117:153–163

    Article  CAS  PubMed  Google Scholar 

  17. Plotnikov NV, Prasad BR, Chakrabarty S, Chu ZT, Warshel A (2013) J Phys Chem B 117:12807–12819

    Article  CAS  PubMed  Google Scholar 

  18. Salvio R, Casnati A (2017) J Org Chem 82:10461–10469

    Article  CAS  PubMed  Google Scholar 

  19. Amadei A, Marinelli F, D’Abramo M, D’Alessandro M, Anselmi M, Di Nola A, Aschi M (2005) J Chem Phys 122:124506

    Article  CAS  PubMed  Google Scholar 

  20. D’Abramo M, Aschi M, Amadei A (2014) J Chem Phys 140:164104

    Article  CAS  PubMed  Google Scholar 

  21. Stoddard BL (2006) Q Rev Biophys 38:49–95

    Article  CAS  Google Scholar 

  22. Dalgaard JZ, Garrett RA, Belfort M (1993) Proc Natl Acad Sci USA 90:5414–5417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Alba J, Marcaida MJ, Prieto J, Montoya G, Molina R, D’Abramo M (2017) J Comput Aided Mol Des 31:1063–1072

    Article  CAS  PubMed  Google Scholar 

  24. Mancin F, Scrimin P, Tecilla P (2012) Chem Commun 48:5545–5559

    Article  CAS  Google Scholar 

  25. Kirby AJ, Medeiros M, Mora JR, Oliveira PS, Amer A, Williams NH, Nome F (2013) J Org Chem 78:1343–1353

    Article  CAS  PubMed  Google Scholar 

  26. Amadei A, D’Alessandro M, Aschi M (2004) J Phys Chem 108:16250–16254

    Article  CAS  Google Scholar 

  27. Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Proteins 78:1950–1958

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Darden T, York D, Pedersen L (1993) J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  29. Bussi G, Donadio D, Parrinello M (2007) J Chem Phys 126:014101

    Article  CAS  PubMed  Google Scholar 

  30. Frisch MJ et al (2009) Gaussian 09, revision D.01. Gaussian Inc., Wallingford CT

    Google Scholar 

  31. Imhof P, Fischer S, Krämer R, Smith JC (2005) J Mol Struct Theochem 713:1–5

    Article  CAS  Google Scholar 

  32. Ribeiro AJM, Ramos MJ, Fernandes PA (2010) J Chem Theory Comput 6:2281–2292

    Article  CAS  PubMed  Google Scholar 

  33. Palermo G, Cavalli A, Klein ML, Alfonso-Prieto M, Dal Peraro M, De Vivo M (2015) Acc Chem Res 48:220–228

    Article  CAS  PubMed  Google Scholar 

  34. Marcaida MJ, Prieto J, Redondo P, Nadra AD, Alibes A, Serrano L, Grizot S, Duchateau P, Paques F, Blanco FJ, Montoya G (2008) Proc Natl Acad Sci USA 105:16888–16893

    Article  PubMed  PubMed Central  Google Scholar 

  35. Molina R, Stella S, Redondo P, Gomez H, Marcaida MJ, Orozco M, Prieto J, Montoya G (2015) Nat Struct Mol Biol 22:65–72

    Article  CAS  PubMed  Google Scholar 

  36. Salvio R, Volpi S, Cacciapaglia R, Sansone F, Mandolini L, Casnati A (2016) J Org Chem 81:4728–4735

    Article  CAS  PubMed  Google Scholar 

  37. Ribeiro AJM, Ramos MJ, Fernandes PA (2012) J Am Chem Soc 134:13436–13447

    Article  CAS  PubMed  Google Scholar 

  38. Pauling L (1947) J Am Chem Soc 69:542–553

    Article  CAS  Google Scholar 

  39. Jencks WP (1972) Chem Rev 72:705–718

    Article  CAS  Google Scholar 

  40. Schrøder Glad S, Jensen F (1997) J Org Chem 62:253–260

    Article  Google Scholar 

  41. Williams NH, Wyman P (2001) Chem Commun 1268–1269

  42. Di Stefano S, Mandolini L (2019) Phys Chem Chem Phys 21:955–978

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially funded by Sapienza, University of Rome (Progetto di Ateneo). The authors gratefully acknowledge NVIDIA and CINECA for computational support. Prof. Luigi Mandolini is acknowledged for helpful discussions.

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Author notes

  1. G.E. Segreto and J. Alba equally contributed to the manuscript.

Authors and Affiliations

  1. Dipartimento di Chimica, “Sapienza” Università di Roma, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Giuseppe E. Segreto, Josephine Alba & Marco D’Abramo

  2. Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy

    Riccardo Salvio

  3. ISB-CNR—UOS Sede di Roma, P.le Aldo Moro 5, 00185, Rome, Italy

    Riccardo Salvio

Authors
  1. Giuseppe E. Segreto
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  2. Josephine Alba
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  3. Riccardo Salvio
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  4. Marco D’Abramo
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Correspondence to Riccardo Salvio or Marco D’Abramo.

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Segreto, G.E., Alba, J., Salvio, R. et al. DNA cleavage by endonuclease I-DmoI: a QM/MM study and comparison with experimental data provide indications on the environmental effects. Theor Chem Acc 139, 68 (2020). https://doi.org/10.1007/s00214-020-2585-0

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  • DOI: https://doi.org/10.1007/s00214-020-2585-0

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