When Water Plays an Active Role in Electronic Structure: Insights from First-Principles Molecular Dynamics Simulations of Biological Systems

  • Giovanni La Penna
Part of the Springer Series in Bio-/Neuroinformatics book series (SSBN, volume 1)


In biological processes, the charge distribution is modified moving electrons and positive holes, mostly protons and metal ions, within hydrated macromolecular assemblies. These events are crucial to transfer the energy of chemical bonds into electric currents and ionic gradients, representing, respectively, energy flow and storage in cells. The modeling of the forces behind these processes is challenging, involving different space and time scales, ranging, at least, from confined electrons to macromolecules in the liquid water environment. Thanks to theoretical advances in first-principles computer simulations and to high performance computers, movements of electrons and transferable cations can be combined into robust and detailed dynamical models. This is also of great help in understanding the role of metal cofactors in important biological processes, like photosynthesis and oxidative stress. This chapter summarizes, through simple examples, statistical applications of density-functional theory, one of the most promising modeling techniques available for this level of description. Particular emphasis is devoted to bridge coarse grained models (built at whatever empirical level) with a refined description of the “reactive” portion of the system involving water molecules.


Water Molecule Polarizable Continuum Model External Potential Ammonium Group Collective Variable 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Guskov, A., Kern, J., Gabdulkhakov, A., Broser, M., Zouni, A., Saenger, W.: Nat. Struct. Mol. Biol. 16, 334 (2009), doi:10.1038/NSMB.1559CrossRefGoogle Scholar
  2. 2.
    Humphrey, W., Dalke, A., Schulten, K.: J. Molec. Graphics 14(1), 33 (1996),, doi:10.1016/0263-7855(96)00018-5CrossRefGoogle Scholar
  3. 3.
    Bertini, I., Gray, H.B., Stiefel, E.I., Valentine, J.S. (eds.): Biological inorganic chemistry: Structure and reactivity. University Science Books (2007)Google Scholar
  4. 4.
    Bryant, R.G., Johnson, M.A., Rossky, P.J.: Acc. Chem. Res. 45(1), 1 (2012), doi:10.1021/ar2003286CrossRefGoogle Scholar
  5. 5.
    Allen, M.P., Tildesley, D.J.: Computer Simulation of Liquids. Clarendon Press, Oxford (1989)Google Scholar
  6. 6.
    Mazza, M.G., Stokely, K., Pagnotta, S.E., Bruni, F., Stanley, H.E., Franzese, G.: Proc. Natl. Acad. Sci. USA 108(50), 19873 (2011), doi:10.1073/pnas.1104299108CrossRefGoogle Scholar
  7. 7.
    Ball, P.: H2O: A biography. Weidenfeld & Nicolson (1999)Google Scholar
  8. 8.
    Lamoureux, G., Roux, B.: J. Chem. Phys. 119(6), 3025 (2003), doi:10.1063/1.1589749CrossRefGoogle Scholar
  9. 9.
    Jiang, W., Hardy, D., Phillips, J., MacKerell, A., Schulten, K., Roux, B.: J. Phys. Chem. Lett. 2, 87 (2011), doi:10.1021/jz101461dCrossRefGoogle Scholar
  10. 10.
    Ponder, J.W., Wu, C., Ren, P., Pande, V.S., Chodera, J.D., Schnieders, M.J., Haque, I., Mobley, D.L., Lambrecht, D.S., Di Stasio, R.A., Head-Gordon, M., Clark, G.N.I., Johnson, M.E., Head-Gordon, T.: J. Phys. Chem. B 114(8), 2549 (2010), doi:10.1021/jp910674dCrossRefGoogle Scholar
  11. 11.
    Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.J.: J. Chem. Phys. 79, 926 (1983), doi:10.1063/1.445869CrossRefGoogle Scholar
  12. 12.
    Parr, R.G., Yang, W.: Density functional theory of atoms and molecules. Oxford University Press, New York (1989)Google Scholar
  13. 13.
    Landau, L., Lifchitz, E.: Physique Statistique. MIR, Moscow (1984)Google Scholar
  14. 14.
    Tomasi, J., Mennucci, B., Cammi, R.: Chem. Rev. 105, 2999 (2005), doi:10.1021/cr9904009CrossRefGoogle Scholar
  15. 15.
    Klamt, A., Mennucci, B., Tomasi, J., Barone, V., Curutchet, C., Orozco, M., Luque, F.J.: Acc. Chem. Res. 42(4), 489 (2009), doi:10.1021/ar800187pCrossRefGoogle Scholar
  16. 16.
    Cramer, C.J., Truhlar, D.G.: Acc. Chem. Res. 42(4), 493 (2009), doi:10.1021/ar900004jCrossRefGoogle Scholar
  17. 17.
    Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Nakai, K.O.H., Vreven, T., Montgomery Jr., J.A., Peralta, J.E., Ogliaro, F., Bearpark, M., Heyd, J.J., Brothers, E., Kudin, K.N., Staroverov, V.N., Keith, T., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Rega, N., Millam, J.M., Klene, M., Knox, J.E., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Martin, R.L., Morokuma, K., Zakrzewski, V.G., Voth, G.A., Salvador, P., Dannenberg, J.J., Dapprich, S., Daniels, A.D., Farkas, O., Foresman, J.B., Ortiz, J.V., Cioslowski, J., Fox, D.J.: Gaussian 09, Revision C.01. Gaussian Inc., Wallingford CT (2010)Google Scholar
  18. 18.
    Muller, N.: Acc. Chem. Res. 23(1), 23 (1990), doi:10.1021/ar00169a005CrossRefGoogle Scholar
  19. 19.
    Ben-Naim, A.: Molecular theory of water and aqueous solutions: Understanding Water. World Scientific (2009)Google Scholar
  20. 20.
    Senn, H.M., Thiel, W.: Angew. Chem. Int. Ed. 48, 1198 (2009)CrossRefGoogle Scholar
  21. 21.
    Barone, V., Improta, R., Rega, N.: Acc. Chem. Res. 41(5), 605 (2008), doi:10.1021/ar7002144CrossRefGoogle Scholar
  22. 22.
    Marx, D., Hutter, J.: Ab initio molecular dynamics: Basic theory and advanced methods. Cambridge University Press, Cambridge (2009)CrossRefGoogle Scholar
  23. 23.
    Pastore, G., Smargiassi, E., Buda, F.: Phys. Rev. A. 44, 6334 (1991), doi:10.1103/PhysRevA.44.6334CrossRefGoogle Scholar
  24. 24.
    Perdew, J.P., Burke, K., Ernzerhof, M.: Phys. Rev. Lett. 77, 3865 (1996)CrossRefGoogle Scholar
  25. 25.
    Becke, A.D.: J. Chem. Phys. 98, 5648 (1993)CrossRefGoogle Scholar
  26. 26.
    Perdew, J.P., Ruzsinszky, A., Csonka, G.I., Vydrov, O.A., Scuseria, G.E., Constantin, L.A., Zhou, X., Burke, K.: Phys. Rev. Lett. 100(13), 136406 (2008)CrossRefGoogle Scholar
  27. 27.
    Schwegler, E., Grossman, J., Gygi, F., Galli, G.: J. Chem. Phys. 121, 5400 (2004)CrossRefGoogle Scholar
  28. 28.
    Schwegler, E., Sharma, M., Gygi, F., Galli, G.: Proc. Natl. Acad. Sci. USA 105(39), 14779 (2008)CrossRefGoogle Scholar
  29. 29.
    Car, R., Parrinello, M.: Phys. Rev. Lett. 55, 2471 (1985)CrossRefGoogle Scholar
  30. 30.
    Wolf, D., Keblinski, P., Phillpot, S.R., Eggebrecht, J.: J. Chem. Phys. 110, 8254 (1999)CrossRefGoogle Scholar
  31. 31.
    Vanderbilt, D.: Phys. Rev. B 41, 7892 (1990)CrossRefGoogle Scholar
  32. 32.
    Giannozzi, P., De Angelis, F., Car, R.: J. Chem. Phys. 120, 5903 (2004)CrossRefGoogle Scholar
  33. 33.
    Knight, C., Voth, G.A.: Acc. Chem. Res. 45(1), 101 (2012), doi:10.1021/ar200140hCrossRefGoogle Scholar
  34. 34.
    Nosé, S.: Molec. Phys. 52, 255 (1984)CrossRefGoogle Scholar
  35. 35.
    Frenkel, D., Smit, B.: Understanding Molecular Simulation. Academic Press, San Diego (1996)zbMATHGoogle Scholar
  36. 36.
    Wales, D.J.: Energy landscapes. Cambridge University Press, Cambridge (2003)Google Scholar
  37. 37.
    Laio, A., Gervasio, F.L.: Rep. Prog. Phys. 71, 126601 (2008), doi: 10.1088/0034-4885/71/12/126601CrossRefGoogle Scholar
  38. 38.
    Łuczkowski, M., Kozłowski, H., Stawikowski, M., Rolka, K., Gaggelli, E., Valensin, D., Valensin, G.: J. Chem. Soc., Dalton Trans. 2002, 2269 (2002), doi:10.1039/B201040MCrossRefGoogle Scholar
  39. 39.
    Burns, C.S., Aronoff-Spencer, E., Dunham, C.M., Lario, P., Avdievich, N.I., Antholine, W.E., Olmstead, M.M., Vrielink, A., Gerfen, G.J., Peisach, J., Scott, W.G., Millhauser, G.L.: Biochemistry 41, 3991 (2002)CrossRefGoogle Scholar
  40. 40.
    Miura, T., Suzuki, K., Kohata, N., Takeuchi, H.: Biochemistry 39(23), 7024 (2000), doi:10.1021/bi0002479CrossRefGoogle Scholar
  41. 41.
    Furlan, S., La Penna, G., Guerrieri, F., Morante, S., Rossi, G.: J. Biol. Inorg. Chem. 12, 571 (2007)CrossRefGoogle Scholar
  42. 42.
    Furlan, S., La Penna, G.: Coord. Chem. Rev. (2012), doi:10.1016/j.ccr.2012.03.036Google Scholar
  43. 43.
    Hureau, C., Balland, V., Coppel, Y., Solari, P.L., Fonda, E., Faller, P.: J. Biol. Inorg. Chem. 14, 995 (2009)CrossRefGoogle Scholar
  44. 44.
    Furlan, S., La Penna, G., Perico, A.: Macromolecules 41, 2938 (2008)CrossRefGoogle Scholar
  45. 45.
    Miller, Y., Ma, B., Nussinov, R.: Proc. Natl. Acad. Sci. USA 107(21), 9490 (2010), doi:10.1073/pnas.0913114107CrossRefGoogle Scholar
  46. 46.
    Furlan, S., Hureau, C., Faller, P., La Penna, G.: J. Phys. Chem. B 114, 15119 (2010)CrossRefGoogle Scholar
  47. 47.
    Giannozzi, P., Baroni, S., Bonini, N., Calandra, M., Car, R., Cavazzoni, C., Ceresoli, D., Chiarotti, G.L., Cococcioni, M., Dabo, I., Dal Corso, A., de Gironcoli, S., Fabris, S., Fratesi, G., Gebauer, R., Gerstmann, U., Gougoussis, C., Kokalj, A., Lazzeri, M., Martin-Samos, L., Marzari, N., Mauri, F., Mazzarello, R., Paolini, S., Pasquarello, A., Paulatto, L., Sbraccia, C., Scandolo, S., Sclauzero, G., Seitsonen, A.P., Smogunov, A., Paolo, U., Wentzcovitch, R.M.: J. Phys.: Condens. Matter 21, 395502 (2009),, doi:10.1088/0953-8984/21/39/395502CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute for Chemistry of Organo-Metallic CompoundsNational Research Council of ItalySesto fiorentino (Firenze)Italy

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