We examine dynamics of water molecules and hydrogen bonds at the water-protein interface of the wild-type antifreeze protein from spruce budworm Choristoneura fumiferana and a mutant that is not antifreeze active by all-atom molecular dynamics simulations. Water dynamics in the hydration layer around the protein is analyzed by calculation of velocity autocorrelation functions and their power spectra, and hydrogen bond time correlation functions are calculated for hydrogen bonds between water molecules and the protein. Both water and hydrogen bond dynamics from subpicosecond to hundred picosecond time scales are sensitive to location on the protein surface and appear correlated with protein function. In particular, hydrogen bond lifetimes are longest for water molecules hydrogen bonded to the ice-binding plane of the wild type, whereas hydrogen bond lifetimes between water and protein atoms on all three planes are similar for the mutant. 1. Introduction While the complex dynamics of large biological molecules and the connection to function have fascinated physical scientists for some time, in more recent years researchers have turned their attention to the interface of biomolecules with water. Coupling of protein and water dynamics, for example, has been examined by molecular simulations [1–10] and a growing number of experimental probes [11–14], and a wide variety of dynamical time scales have been found [15, 16] due to the heterogeneity of protein-water interactions. One class of proteins for which protein-water interactions are critical to function is antifreeze proteins (AFPs). AFPs are widely distributed in certain plants, vertebrates, fungi, and bacteria to provide cells protection in cold environments [17–20] but the mechanism for antifreeze activity is still not well understood. In this paper we analyze by all-atom molecular dynamics (MD) simulations the dynamics of water molecules and hydrogen bonds at the protein-water interface of the AFP from the spruce budworm Choristoneura fumiferana and a mutant that has little antifreeze activity. We calculate velocity autocorrelation functions and their power spectra for water molecules around the protein and we compute hydrogen bond time correlation functions for bonds between the protein and water. We obtain distinct spectra for the water around different regions of the protein, which are affected by mutation. Moreover, we observe longer hydrogen bonding between water molecules and the ice-binding plane of this AFP compared to other parts of the protein, a difference that nearly disappears with
References
[1]
D. J. Tobias, N. Sengupta, and M. Tarek, “Molecular dynamics simulation studies of coupled protein and water dynamics,” in Proteins: Energy, Heat and Signal Flow, D. M. Leitner and J. E. Straub, Eds., pp. 361–386, Taylor & Francis, Boca Raton, Fla, USA, 2009.
[2]
M. E. Johnson, C. Malardier-Jugroot, R. K. Murarka, and T. Head-Gordon, “Hydration water dynamics near biological interfaces,” Journal of Physical Chemistry B, vol. 113, no. 13, pp. 4082–4092, 2009.
[3]
A. R. Bizzarri and S. Cannistraro, “Molecular dynamics of water at the protein-solvent interface,” Journal of Physical Chemistry B, vol. 106, no. 26, pp. 6617–6633, 2002.
[4]
P. J. Steinbach and B. R. Brooks, “Protein hydration elucidated by molecular dynamics simulation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 19, pp. 9135–9139, 1993.
[5]
D. N. LeBard and D. V. Matyushov, “Ferroelectric hydration shells around proteins: electrostatics of the protein-water interface,” Journal of Physical Chemistry B, vol. 114, no. 28, pp. 9246–9258, 2010.
[6]
X. Yu, J. Park, and D. M. Leitner, “Thermodynamics of protein hydration computed by molecular dynamics and normal modes,” Journal of Physical Chemistry B, vol. 107, no. 46, pp. 12820–12828, 2003.
[7]
F. Despa, A. Fernández, and R. S. Berry, “Publisher's note—dielectric modulation of biological water,” Physical Review Letters, vol. 93, no. 26, Article ID 228104, 1 pages, 2004.
[8]
R. Gnanasekaran, J. K. Agbo, and D. M. Leitner, “Communication maps computed for homodimeric hemoglobin: computational study of water-mediated energy transport in proteins,” Journal of Chemical Physics, vol. 135, no. 6, Article ID 065103, 10 pages, 2011.
[9]
R. Gnanasekaran, Y. Xu, and D. M. Leitner, “Dynamics of water clusters confined in proteins: a molecular dynamics simulation study of interfacial waters in a dimeric hemoglobin,” Journal of Physical Chemistry B, vol. 114, no. 50, pp. 16989–16996, 2010.
[10]
A. Lervik, F. Bresme, S. Kjelstrup, D. Bedeaux, and J. M. Rubi, “Heat transfer in protein-water interfaces,” Physical Chemistry Chemical Physics, vol. 12, no. 7, pp. 1610–1617, 2010.
[11]
D. M. Leitner, M. Havenith, and M. Gruebele, “Biomolecule large-amplitude motion and solvation dynamics: modelling and probes from THz to X-rays,” International Reviews in Physical Chemistry, vol. 25, no. 4, pp. 553–582, 2006.
[12]
L. Mitra, N. Smolin, R. Ravindra, C. Royer, and R. Winter, “Pressure perturbation calorimetric studies of the solvation properties and the thermal unfolding of proteins in solution—experiments and theoretical interpretation,” Physical Chemistry Chemical Physics, vol. 8, no. 11, pp. 1249–1265, 2006.
[13]
S. K. Pal, J. Peon, and A. H. Zewail, “Biological water at the protein surface: dynamical solvation probed directly with femtosecond resolution,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 4, pp. 1763–1768, 2002.
[14]
W. Doster and M. Settles, “The dynamical transition in proteins: the role of hydrogen bonds,” in Hydration Processes in Biology: Experimental and Theoretical Approaches, M.-C. Bellissent-Funel, Ed., pp. 177–195, IOS Press, Amsterdam, The Netherlands, 1999.
[15]
E. Persson and B. Halle, “Cell water dynamics on multiple time scales,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 17, pp. 6266–6271, 2008.
[16]
H. Frauenfelder, P. W. Fenimore, G. Chen, and B. H. McMahon, “Protein folding is slaved to solvent motions,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 42, pp. 15469–15472, 2006.
[17]
S. P. Graether, Biochemistry and Function of Antifreeze Proteins, Nova Science, New York, NY, USA, 2011.
[18]
J. G. Duman, K. R. Walters, T. Sformo, et al., “Antifreeze and ice-nucleator proteins,” in Low Temperature Biology of Insects, D. L. Delinger and R. E. Lee, Eds., pp. 59–90, Cambridge University Press, New York, NY, USA, 2010.
[19]
B. Moffatt, V. Ewart, and A. Eastman, “Cold comfort: plant antifreeze proteins,” Physiologia Plantarum, vol. 126, no. 1, pp. 5–16, 2006.
[20]
L. Pham, R. Dahiya, and B. Rubinsky, “An in vivo study of antifreeze protein adjuvant cryosurgery,” Cryobiology, vol. 38, no. 2, pp. 169–175, 1999.
[21]
A. L. DeVries and D. E. Wohlschlag, “Freezing resistance in some antarctic fishes,” Science, vol. 163, no. 3871, pp. 1073–1075, 1969.
[22]
J. A. Raymond and A. L. DeVries, “Adsorption inhibition as a mechanism of freezing resistance in polar fishes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 74, no. 6, pp. 2589–2593, 1977.
[23]
J. A. Raymond, P. W. Wilson, and A. L. DeVries, “Inhibition of growth of nonbasal planes in ice by fish antifreezes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 3, pp. 881–885, 1989.
[24]
C. A. Knight, C. C. Cheng, and A. L. DeVries, “Adsorption of α-helical antifreeze peptides on specific ice crystal surface planes,” Biophysical Journal, vol. 59, no. 2, pp. 409–418, 1991.
[25]
J. Duman and A. L. DeVries, “Isolation, characterization, and physical properties of protein antifreezes from the winter flounder, pseudopleuronectes americanus,” Comparative Biochemistry and Physiology, vol. 54, no. 3, pp. 375–380, 1976.
[26]
A. D. Haymet, L. G. Ward, M. M. Harding, and C. A. Knight, “Valine substituted winter flounder “antifreeze”: preservation of ice growth hysteresis,” FEBS Letters, vol. 430, no. 3, pp. 301–306, 1998.
[27]
S. Ebbinghaus, K. Meister, B. Born, A. L. Devries, M. Gruebele, and M. Havenith, “Antifreeze glycoprotein activity correlates with long-range protein-water dynamics,” Journal of the American Chemical Society, vol. 132, no. 35, pp. 12210–12211, 2010.
[28]
S. P. Graether, M. J. Kuiper, and S. M. Gagne, “Beta-helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect,” Nature, pp. 325–328, 2000.
[29]
D. R. Nutt and J. C. Smith, “Dual function of the hydration layer around an antifreeze protein revealed by atomistic molecular dynamics simulations,” Journal of the American Chemical Society, vol. 130, no. 39, pp. 13066–13073, 2008.
[30]
N. Guex and M. C. Peitsch, “SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling,” Electrophoresis, vol. 18, no. 15, pp. 2714–2723, 1997.
[31]
Y. Duan, C. Wu, S. Chowdhury et al., “A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations,” Journal of Computational Chemistry, vol. 24, no. 16, pp. 1999–2012, 2003.
[32]
H. J. C. Berendsen, D. Spoel, and R. V. Drunen, “GROMACS: a message-passing parallel molecular dynamics implementation,” Computer Physics Communications, vol. 91, no. 1–3, pp. 43–56, 1995.
[33]
X. Yu and D. M. Leitner, “Vibrational energy transfer and heat conduction in a protein,” Journal of Physical Chemistry B, vol. 107, no. 7, pp. 1698–1707, 2003.
[34]
X. Yu and D. M. Leitner, “Anomalous diffusion of vibrational energy in proteins,” Journal of Chemical Physics, vol. 119, no. 23, pp. 12673–12679, 2003.
[35]
X. Yu and D. M. Leitner, “Heat flow in proteins: computation of thermal transport coefficients,” Journal of Chemical Physics, vol. 122, no. 5, Article ID 054902, 11 pages, 2005.
[36]
D. M. Leitner, “Vibrational energy transfer and heat conduction in a one-dimensional glass,” Physical Review B, vol. 64, no. 9, Article ID 094201, 9 pages, 2001.
[37]
B. Bagchi, “Water dynamics in the hydration layer around proteins and micelles,” Chemical Reviews, vol. 105, no. 9, pp. 3197–3219, 2005.
[38]
M. Tarek and D. J. Tobias, “Role of protein-water hydrogen bond dynamics in the protein dynamical transition,” Physical Review Letters, vol. 88, no. 13, Article ID 138101, 4 pages, 2002.
[39]
A. Luzar and D. Chandler, “Hydrogen-bond kinetics in liquid water,” Nature, vol. 379, no. 6560, pp. 55–57, 1996.
[40]
M. Heyden and M. Havenith, “Combining THz spectroscopy and MD simulations to study protein-hydration coupling,” Methods, vol. 52, no. 1, pp. 74–83, 2010.
[41]
S. Bandyopadhyay, S. Chakraborty, and B. Bagchi, “Secondary structure sensitivity of hydrogen bond lifetime dynamics in the protein hydration layer,” Journal of the American Chemical Society, vol. 127, no. 47, pp. 16660–16667, 2005.
[42]
G. E. Walrafen and Y. C. Chu, “Linearity between structural correlation length and correlated-proton Raman intensity from amorphous ice and supercooled water up to dense supercritical steam,” Journal of Physical Chemistry, vol. 99, no. 28, pp. 11225–11229, 1995.
[43]
G. E. Walrafen, Y. C. Chu, and G. J. Piermarini, “Low-frequency Raman scattering from water at high pressures and high temperatures,” Journal of Physical Chemistry, vol. 100, no. 24, pp. 10363–10372, 1996.
[44]
S. Chakraborty, S. K. Sinha, and S. Bandyopadhyay, “Low-frequency vibrational spectrum of water in the hydration layer of a protein: a molecular dynamics simulation study,” Journal of Physical Chemistry B, vol. 111, no. 48, pp. 13626–13631, 2007.
[45]
Y. Xu, R. Gnanasekaran, and D. M. Leitner, (to be published).
[46]
N. Nandi and B. Bagchi, “Dielectric relaxation of biological water,” Journal of Physical Chemistry B, vol. 101, no. 50, pp. 10954–10961, 1997.
[47]
S. K. Pal, J. Peon, B. Bagchi, and A. H. Zewail, “Biological water: femtosecond dynamics of macromolecular hydration,” Journal of Physical Chemistry B, vol. 106, no. 48, pp. 12376–12395, 2002.
[48]
S. Ebbinghaus, S. J. Kim, M. Heyden et al., “An extended dynamical hydration shell around proteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 52, pp. 20749–20752, 2007.
[49]
S. Ebbinghaus, S. J. Kim, M. Heyden et al., “Protein sequence- and pH-dependent hydration probed by terahertz spectroscopy,” Journal of the American Chemical Society, vol. 130, no. 8, pp. 2374–2375, 2008.
[50]
A. D. Friesen and D. V. Matyushov, “Non-Gaussian statistics of electrostatic fluctuations of hydration shells,” Journal of Chemical Physics, vol. 135, no. 10, Article ID 104501, 7 pages, 2011.
[51]
B. Born, S. J. Kim, S. Ebbinghaus, M. Gruebele, and M. Havenith, “The terahertz dance of water with the proteins: the effect of protein flexibility on the dynamical hydration shell of ubiquitin,” Faraday Discussions, vol. 141, pp. 161–173, 2008.
[52]
U. Heugen, G. Schwaab, E. Bründermann et al., “Solute-induced retardation of water dynamics probed directly by terahertz spectroscopy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 33, pp. 12301–12306, 2006.
[53]
M. Heyden, E. Bründermann, U. Heugen, G. Niehues, D. M. Leitner, and M. Havenith, “Long-range influence of carbohydrates on the solvation dynamics of water—answers from terahertz absorption measurements and molecular modeling simulations,” Journal of the American Chemical Society, vol. 130, no. 17, pp. 5773–5779, 2008.
[54]
J. Knab, J. Y. Chen, and A. G. Markelz, “Hydration dependence of conformational dielectric relaxation of lysozyme,” Biophysical Journal, vol. 90, no. 7, pp. 2576–2581, 2006.
[55]
N. Q. Vinh, S. J. Allen, and K. W. Plaxco, “Dielectric spectroscopy of proteins as a quantitative experimental test of computational models of their low-frequency harmonic motions,” Journal of the American Chemical Society, vol. 133, no. 23, pp. 8942–8947, 2011.
