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Parmbsc1: a refined force field for DNA simulations

Abstract

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of 140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/.

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Figure 1: Analysis of the DDD.
Figure 2: Analysis of noncanonical DNA structures.
Figure 3: Analysis of DNA-protein complexes.

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References

  1. 1

    Pérez, A., Luque, F.J. & Orozco, M. Acc. Chem. Res. 45, 196–205 (2012).

    PubMed  Google Scholar 

  2. 2

    Pérez, A., Luque, F.J. & Orozco, M. J. Am. Chem. Soc. 129, 14739–14745 (2007).

    PubMed  Google Scholar 

  3. 3

    Várnai, P. & Zakrzewska, K. Nucleic Acids Res. 32, 4269–4280 (2004).

    PubMed  PubMed Central  Google Scholar 

  4. 4

    Pérez, A. et al. Biophys. J. 92, 3817–3829 (2007).

    PubMed  PubMed Central  Google Scholar 

  5. 5

    Zgarbová, M. et al. J. Chem. Theory Comput. 9, 2339–2354 (2013).

    PubMed  PubMed Central  Google Scholar 

  6. 6

    Krepl, M. et al. J. Chem. Theory Comput. 8, 2506–2520 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Wing, R. et al. Nature 287, 755–758 (1980).

    CAS  PubMed  Google Scholar 

  8. 8

    Lavery, R. et al. Nucleic Acids Res. 38, 299–313 (2010).

    CAS  PubMed  Google Scholar 

  9. 9

    Dans, P.D., Pérez, A., Faustino, I., Lavery, R. & Orozco, M. Nucleic Acids Res. 40, 10668–10678 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Lankaš, F., Špačková, N., Moakher, M., Enkhbayar, P. & Šponer, J. Nucleic Acids Res. 38, 3414–3422 (2010).

    PubMed  PubMed Central  Google Scholar 

  11. 11

    Thamann, T.J., Lord, R.C., Wang, A.H.J. & Rich, A. Nucleic Acids Res. 9, 5443–5458 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Abrescia, N.G.A., González, C., Gouyette, C. & Subirana, J.A. Biochemistry 43, 4092–4100 (2004).

    CAS  PubMed  Google Scholar 

  13. 13

    Cubero, E., Luque, F.J. & Orozco, M. J. Am. Chem. Soc. 123, 12018–12025 (2001).

    CAS  PubMed  Google Scholar 

  14. 14

    Soyfer, V.N. & Potaman, V.N. Triple-helical Nucleic Acids 1st edn. (Springer-Verlag, 1996).

  15. 15

    Fadrná, E. et al. J. Chem. Theory Comput. 5, 2514–2530 (2009).

    PubMed  Google Scholar 

  16. 16

    Martín-Pintado, N. et al. J. Am. Chem. Soc. 135, 5344–5347 (2013).

    PubMed  Google Scholar 

  17. 17

    Olson, W.K., Gorin, A.A., Lu, X.-J., Hock, L.M. & Zhurkin, V.B. Proc. Natl. Acad. Sci. USA 95, 11163–11168 (1998).

    CAS  PubMed  Google Scholar 

  18. 18

    Pérez, A., Lankas, F., Luque, F.J. & Orozco, M. Nucleic Acids Res. 36, 2379–2394 (2008).

    PubMed  PubMed Central  Google Scholar 

  19. 19

    Moroz, J.D. & Nelson, P. Proc. Natl. Acad. Sci. USA 94, 14418–14422 (1997).

    CAS  PubMed  Google Scholar 

  20. 20

    Du, Q., Kotlyar, A. & Vologodskii, A. Nucleic Acids Res. 36, 1120–1128 (2008).

    CAS  PubMed  Google Scholar 

  21. 21

    Šponer, J., Jurecka, P. & Hobza, P. J. Am. Chem. Soc. 126, 10142–10151 (2004).

    PubMed  Google Scholar 

  22. 22

    Hobza, P., Kabeláč, M., Šponer, J., Mejzlík, P. & Vondrášek, J. J. Comput. Chem. 18, 1136–1150 (1997).

    CAS  Google Scholar 

  23. 23

    Šponer, J. et al. Chemistry 12, 2854–2865 (2006).

    PubMed  Google Scholar 

  24. 24

    Orozco, M. & Luque, F.J. Chem. Phys. 182, 237–248 (1994).

    CAS  Google Scholar 

  25. 25

    Colominas, C., Luque, F.J. & Orozco, M. J. Am. Chem. Soc. 118, 6811–6821 (1996).

    CAS  Google Scholar 

  26. 26

    Orozco, M., Cubero, E., Hernández, B., López, J.M. & Luque, F.J. in Computational Chemistry: Reviews of Current Trends Vol. 4 (ed. Leszczynski, J.) 191–225 (World Scientific Publishing, 1999).

  27. 27

    Pérez, A. et al. Chemistry 11, 5062–5066 (2005).

    PubMed  Google Scholar 

  28. 28

    Beveridge, D.L. et al. Biophys. J. 87, 3799–3813 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Portella, G., Germann, M.W., Hud, N.V. & Orozco, M. J. Am. Chem. Soc. 136, 3075–3086 (2014).

    CAS  PubMed  Google Scholar 

  30. 30

    Krishnan, R., Binkley, J.S., Seeger, R. & Pople, J.A. J. Chem. Phys. 72, 650–654 (1980).

    CAS  Google Scholar 

  31. 31

    Woon, D.E. & Dunning, T.H. Jr. J. Chem. Phys. 98, 1358–1371 (1993).

    CAS  Google Scholar 

  32. 32

    Halkier, A. et al. Chem. Phys. Lett. 286, 243–252 (1998).

    CAS  Google Scholar 

  33. 33

    Halkier, A., Helgaker, T., Jørgensen, P., Klopper, W. & Olsen, J. Chem. Phys. Lett. 302, 437–446 (1999).

    CAS  Google Scholar 

  34. 34

    Miertuš, S., Scrocco, E. & Tomasi, J. Chem. Phys. 55, 117–129 (1981).

    Google Scholar 

  35. 35

    Miertuš, S. & Tomasi, J. Chem. Phys. 65, 239–245 (1982).

    Google Scholar 

  36. 36

    Cancès, E., Mennucci, B. & Tomasi, J. J. Chem. Phys. 107, 3032–3041 (1997).

    Google Scholar 

  37. 37

    Bachs, M., Luque, F.J. & Orozco, M. J. Comput. Chem. 15, 446–454 (1994).

    CAS  Google Scholar 

  38. 38

    Soteras, I., Curutchet, C., Bidon-Chanal, A., Orozco, M. & Luque, F.J. J. Mol. Struct. THEOCHEM 727, 29–40 (2005).

    CAS  Google Scholar 

  39. 39

    Soteras, I., Forti, F., Orozco, M. & Luque, F.J. J. Phys. Chem. B 113, 9330–9334 (2009).

    CAS  PubMed  Google Scholar 

  40. 40

    Soteras, I., Orozco, M. & Luque, F.J. J. Comput. Aided Mol. Des. 24, 281–291 (2010).

    CAS  PubMed  Google Scholar 

  41. 41

    Marenich, A.V., Cramer, C.J. & Truhlar, D.G. J. Phys. Chem. B 113, 6378–6396 (2009).

    CAS  Google Scholar 

  42. 42

    Torrie, G.M. & Valleau, J.P. J. Comput. Phys. 23, 187–199 (1977).

    Google Scholar 

  43. 43

    Hart, K. et al. J. Chem. Theory Comput. 8, 348–362 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Wu, Z., Delaglio, F., Tjandra, N., Zhurkin, V.B. & Bax, A. J. Biomol. NMR 26, 297–315 (2003).

    CAS  PubMed  Google Scholar 

  45. 45

    Zgarbová, M. et al. J. Chem. Theory Comput. 7, 2886–2902 (2011).

    PubMed  PubMed Central  Google Scholar 

  46. 46

    Hess, B., Kutzner, C., Van Der Spoel, D. & Lindahl, E. J. Chem. Theory Comput. 4, 435–447 (2008).

    CAS  Google Scholar 

  47. 47

    Galindo-Murillo, R., Roe, D.R. & Cheatham, T.E. III. Nat. Commun. 5, 5152 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Ryckaert, J.-P., Ciccotti, G. & Berendsen, H.J.C. J. Comput. Phys. 23, 327–341 (1977).

    CAS  Google Scholar 

  49. 49

    Hess, B., Bekker, H., Berendsen, H.J.C. & Fraaije, J.G.E.M. J. Comput. Chem. 18, 1463–1472 (1997).

    CAS  Google Scholar 

  50. 50

    Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W. & Klein, M.L. J. Chem. Phys. 79, 926–935 (1983).

    CAS  Google Scholar 

  51. 51

    Berendsen, H.J.C., Grigera, J.R. & Straatsma, T.P. J. Phys. Chem. 91, 6269–6271 (1987).

    CAS  Google Scholar 

  52. 52

    Smith, D.E. & Dang, L.X. J. Chem. Phys. 100, 3757–3766 (1994).

    CAS  Google Scholar 

  53. 53

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

    CAS  Google Scholar 

  54. 54

    Liu, C., Janowski, P.A. & Case, D.A. Biochim. Biophys. Acta 1850, 1059–1071 (2015).

    CAS  PubMed  Google Scholar 

  55. 55

    Arnott, S. & Hukins, D.W.L. Biochem. Biophys. Res. Commun. 47, 1504–1509 (1972).

    CAS  PubMed  Google Scholar 

  56. 56

    Orozco, M., Pérez, A., Noy, A. & Luque, F.J. Chem. Soc. Rev. 32, 350–364 (2003).

    CAS  PubMed  Google Scholar 

  57. 57

    Pérez, A. et al. J. Chem. Theory Comput. 1, 790–800 (2005).

    PubMed  Google Scholar 

  58. 58

    Amadei, A., Linssen, A. & Berendsen, H.J.C. Proteins 17, 412–425 (1993).

    CAS  PubMed  Google Scholar 

  59. 59

    Lankaš, F., Šponer, J., Hobza, P. & Langowski, J. J. Mol. Biol. 299, 695–709 (2000).

    PubMed  Google Scholar 

  60. 60

    Noy, A., Perez, A., Lankas, F., Luque, F.J. & Orozco, M. J. Mol. Biol. 343, 627–638 (2004).

    CAS  PubMed  Google Scholar 

  61. 61

    Andricioaei, I. & Karplus, M. J. Chem. Phys. 115, 6289–6292 (2001).

    CAS  Google Scholar 

  62. 62

    Schlitter, J. Chem. Phys. Lett. 215, 617–621 (1993).

    CAS  Google Scholar 

  63. 63

    Hess, B. Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 62, 8438 (2000).

    CAS  PubMed  Google Scholar 

  64. 64

    Noy, A. & Golestanian, R. Phys. Rev. Lett. 109, 228101 (2012).

    PubMed  Google Scholar 

  65. 65

    Zheng, G., Czapla, L., Srinivasan, A.R. & Olson, W.K. Phys. Chem. Chem. Phys. 12, 1399–1406 (2010).

    CAS  PubMed  Google Scholar 

  66. 66

    Cuervo, A. et al. Proc. Natl. Acad. Sci. USA 111, E3624–E3630 (2014).

    CAS  PubMed  Google Scholar 

  67. 67

    Yang, L., Weerasinghe, S., Smith, P.E. & Pettitt, P.M. Biophys. J. 69, 1519–1527 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Hospital, A. et al. Bioinformatics 28, 1278–1279 (2012).

    CAS  PubMed  Google Scholar 

  69. 69

    Hospital, A. et al. Nucleic Acids Res. 41, W47–W55 (2013).

    PubMed  PubMed Central  Google Scholar 

  70. 70

    Lavery, R., Moakher, M., Maddocks, J.H., Petkeviciute, D. & Zakrzewska, K. Nucleic Acids Res. 37, 5917–5929 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Zweckstetter, M. Nat. Protoc. 3, 679–690 (2008).

    CAS  PubMed  Google Scholar 

  72. 72

    Bernstein, F.C. et al. Eur. J. Biochem. 80, 319–324 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Borgias, B.A. & James, T.L. J. Magn. Reson. 87, 475–487 (1990).

    CAS  Google Scholar 

  74. 74

    Mobley, D.L., Chodera, J.D. & Dill, K.A. J. Chem. Phys. 125, 084902 (2006).

    PubMed  PubMed Central  Google Scholar 

  75. 75

    Sousa da Silva, A.W. & Vranken, W.F. BMC Res. Notes 5, 367 (2012).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

M.O. thanks the Spanish Ministry of Science (BIO2012-32868), the Catalan SGR, the Instituto Nacional de Bioinformática and the European Research Council (ERC SimDNA) for support. M.O. is an academia researcher in the Catalan Institution for Research and Advanced Studies (ICREA). M.O. thanks the Barcelona Supercomputing Center for CPU and GPU time on MareNostrum and MinoTauro. C.A.L., S.A.H. and A.N. thank the UK HECBioSim Consortium for time on the ARCHER high-performance computing system (grant EP-L000253-1). A.N. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC; grant BB-I019294-1) and thanks ARC Leeds for computational resources. P.D.D. is a PEDECIBA (Programa de Desarrollo de las Ciencias Básicas) and SNI (Sistema Nacional de Investigadores; ANII, Uruguay) researcher. D.A.C. thanks C. Liu for assistance with the crystal simulation analysis.

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Contributions

I.I. derived the parmbsc1 force-field parameter set. I.I., P.D.D., A.N., A.P., I.F., A.H., J.W., A.B., G.P., F.B., C.A.L. and S.A.H. performed validation simulations. C.G., M.V. and G.P. validated results from NMR-based experiments. C.G. obtained de novo NMR spectroscopy measurements. D.A.C. performed crystal MD simulations. R.G., P.A., A.H. and J.L.G. created the database infrastructure and web application. All authors contributed to data analysis. M.O. had the idea for the study, directed the project and wrote the manuscript, which was improved by the rest of the authors.

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Correspondence to Modesto Orozco.

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The authors declare no competing financial interests.

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Supplementary Figures 1–31, Supplementary Tables 1–12 and Supplementary Discussion (PDF 5701 kb)

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Parmbsc1 parameters (ZIP 13 kb)

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Ivani, I., Dans, P., Noy, A. et al. Parmbsc1: a refined force field for DNA simulations. Nat Methods 13, 55–58 (2016). https://doi.org/10.1038/nmeth.3658

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