Protein dynamics tightly connected to the dynamics of surrounding and internal water molecules.

Proteins are key components of biological cells. For example, enzymes catalyze biochemical reactions, membrane transporters are responsible for uptake and release of critical and superfluous components from the cell environment, and structural proteins are responsible for the stability of the cell wall and cytoskeleton. Many of the diverse protein functions involve dynamic transitions ranging from small local atomic displacements up to large allosteric conformational changes. In any conformation, proteins are in contact with the universal solvent medium of cells, water. Water not only surrounds proteins but is often an integral part of proteins and also is involved in key mechanistic steps. This Minireview discusses recent experimental and theoretical results on the role of water for protein dynamics and function.

[1]  B M Pettitt,et al.  A Connected‐cluster of hydration around myoglobin: Correlation between molecular dynamics simulations and experiment , 1994, Proteins.

[2]  Donald Hamelberg,et al.  Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method. , 2004, Journal of the American Chemical Society.

[3]  M. Lill,et al.  Proton shuttle in green fluorescent protein studied by dynamic simulations , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Bagchi,et al.  Slow dynamics of constrained water in complex geometries , 2000 .

[5]  H. Frauenfelder,et al.  Slaving: Solvent fluctuations dominate protein dynamics and functions , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H Luecke,et al.  Structure of bacteriorhodopsin at 1.55 A resolution. , 1999, Journal of molecular biology.

[7]  J. Hermans,et al.  The Free Energy of Xenon Binding to Myoglobin from Molecular Dynamics Simulation , 1986 .

[8]  J Andrew McCammon,et al.  Structural and dynamic properties of water around acetylcholinesterase , 2002, Protein science : a publication of the Protein Society.

[9]  Dominik Marx,et al.  Proton transfer 200 years after von Grotthuss: insights from ab initio simulations. , 2006, Chemphyschem : a European journal of chemical physics and physical chemistry.

[10]  B. Halle,et al.  Using buried water molecules to explore the energy landscape of proteins , 1996, Nature Structural Biology.

[11]  B. L. de Groot,et al.  The mechanism of proton exclusion in the aquaporin-1 water channel. , 2003, Journal of molecular biology.

[12]  Richard A. L. Jones Soft Condensed Matter , 2002 .

[13]  H. Berendsen,et al.  Essential dynamics of proteins , 1993, Proteins.

[14]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[15]  R C Wade,et al.  Hydration energy landscape of the active site cavity in cytochrome P450cam , 1998, Proteins.

[16]  Salvatore Cannistraro,et al.  Molecular Dynamics of Water at the Protein-Solvent Interface , 2002 .

[17]  Gerhard Hummer,et al.  Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  B. Halle,et al.  Water dynamics in the large cavity of three lipid-binding proteins monitored by (17)O magnetic relaxation dispersion. , 2003, Journal of molecular biology.

[19]  Bertrand Guillot,et al.  A reappraisal of what we have learnt during three decades of computer simulations on water , 2002 .

[20]  D. Agard,et al.  The 0.83 A resolution crystal structure of alpha-lytic protease reveals the detailed structure of the active site and identifies a source of conformational strain. , 2004, Journal of molecular biology.

[21]  Aliaksei Krukau,et al.  Percolation transition of hydration water: from planar hydrophilic surfaces to proteins. , 2005, Physical review letters.

[22]  J. M. Lluch,et al.  Potential energy landscape of the photoinduced multiple proton-transfer process in the green fluorescent protein: classical molecular dynamics and multiconfigurational electronic structure calculations. , 2006, Journal of the American Chemical Society.

[23]  Jeremy C. Smith,et al.  Translational hydration water dynamics drives the protein glass transition. , 2003, Biophysical journal.

[24]  Jeremy C. Smith,et al.  Thermodynamic stability of water molecules in the bacteriorhodopsin proton channel: a molecular dynamics free energy perturbation study. , 1996, Biophysical journal.

[25]  P. Argos,et al.  Cavities and packing at protein interfaces , 1994, Protein science : a publication of the Protein Society.

[26]  J. Dunitz The entropic cost of bound water in crystals and biomolecules. , 1994, Science.

[27]  P. Goodford A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. , 1985, Journal of medicinal chemistry.

[28]  R. Friesner,et al.  Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic catalysis. , 2005, Annual review of physical chemistry.

[29]  M. Grütter,et al.  Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Michael H. Mazor,et al.  Hydration of cavities in proteins : a molecular dynamics approach , 1990 .

[31]  M. Bellissent-Funel,et al.  Hydration in protein dynamics and function , 2000 .

[32]  V. Pande,et al.  Can conformational change be described by only a few normal modes? , 2006, Biophysical journal.

[33]  W. Doster,et al.  Protein-water displacement distributions. , 2005, Biochimica et biophysica acta.

[34]  G. Hummer,et al.  Water penetration and escape in proteins , 2000, Proteins.

[35]  P-L Chau Water movement during ligand unbinding from receptor site. , 2004, Biophysical journal.

[36]  Lennart Nilsson,et al.  Molecular origin of time-dependent fluorescence shifts in proteins. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Sheldon Park,et al.  Statistical and molecular dynamics studies of buried waters in globular proteins , 2005, Proteins.

[38]  H Frauenfelder,et al.  Dynamics of ligand binding to myoglobin. , 1975, Biochemistry.

[39]  N. Go,et al.  Effect of solvent on collective motions in globular protein. , 1993, Journal of molecular biology.

[40]  R C Wade,et al.  Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 2. Ligand probe groups with the ability to form more than two hydrogen bonds. , 1993, Journal of medicinal chemistry.

[41]  G. Feher,et al.  Proton transfer pathways and mechanism in bacterial reaction centers , 2003, FEBS letters.

[42]  Jeremy C. Smith,et al.  Principal components of the protein dynamical transition. , 2003, Physical review letters.

[43]  Sharon Hammes-Schiffer,et al.  Impact of distal mutations on the network of coupled motions correlated to hydride transfer in dihydrofolate reductase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  B. Pettitt,et al.  Solvation and hydration of proteins and nucleic acids: a theoretical view of simulation and experiment. , 2002, Accounts of chemical research.

[45]  Greg L. Hura,et al.  Hydration dynamics near a model protein surface. , 2004, Biophysical journal.

[46]  Klaus Gerwert,et al.  Dynamics of water molecules in the bacteriorhodopsin trimer in explicit lipid/water environment. , 2004, Biophysical journal.

[47]  Wilfred F van Gunsteren,et al.  Simulations of apo and holo-fatty acid binding protein: structure and dynamics of protein, ligand and internal water. , 2002, Journal of molecular biology.

[48]  N. Smolin,et al.  Properties of spanning water networks at protein surfaces. , 2005, The journal of physical chemistry. B.

[49]  Michael Feig,et al.  Extending the horizon: towards the efficient modeling of large biomolecular complexes in atomic detail , 2006 .

[50]  Arieh Ben-Naim,et al.  Solvation thermodynamics of nonionic solutes , 1984 .

[51]  Michael W. Mahoney,et al.  Diffusion constant of the TIP5P model of liquid water , 2001 .

[52]  Arieh Warshel,et al.  Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions. , 2006, The journal of physical chemistry. B.

[53]  B. Halle,et al.  Biomolecular hydration: From water dynamics to hydrodynamics , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A M Gronenborn,et al.  Demonstration of positionally disordered water within a protein hydrophobic cavity by NMR. , 1995, Science.

[55]  G. Ullmann,et al.  Internal hydration of protein cavities: studies on BPTI , 2004 .

[56]  Liang Zhao,et al.  Ultrafast hydration dynamics in protein unfolding: human serum albumin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Volkhard Helms,et al.  Molecular dynamics simulation of proton transport with quantum mechanically derived proton hopping rates (Q-HOP MD) , 2001 .

[58]  C. Brooks,et al.  Recent advances in the development and application of implicit solvent models in biomolecule simulations. , 2004, Current opinion in structural biology.

[59]  D. Tobias,et al.  The dynamics of protein hydration water: a quantitative comparison of molecular dynamics simulations and neutron-scattering experiments. , 2000, Biophysical journal.

[60]  J L Sussman,et al.  Open "back door" in a molecular dynamics simulation of acetylcholinesterase. , 1994, Science.

[61]  Gideon Schreiber,et al.  Separating the contribution of translational and rotational diffusion to protein association. , 2005, Journal of the American Chemical Society.

[62]  Ronald M. Welch,et al.  Climatic Impact of Tropical Lowland Deforestation on Nearby Montane Cloud Forests , 2001, Science.

[63]  P. Kollman,et al.  Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices , 1998 .

[64]  W. C. Still,et al.  The GB/SA Continuum Model for Solvation. A Fast Analytical Method for the Calculation of Approximate Born Radii , 1997 .

[65]  Jürgen Köhler,et al.  Direct observation of tiers in the energy landscape of a chromoprotein: A single-molecule study , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[66]  G. Careri,et al.  Protein hydration and function. , 1991, Advances in protein chemistry.

[67]  B. Halle,et al.  Microsecond exchange of internal water molecules in bacteriorhodopsin. , 2001, Journal of molecular biology.

[68]  B. Stec,et al.  On the nature of a glassy state of matter in a hydrated protein: Relation to protein function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Erik F. Y. Hom,et al.  Diffusion of green fluorescent protein in the aqueous-phase lumen of endoplasmic reticulum. , 1999, Biophysical journal.

[70]  J. Antosiewicz,et al.  Effects of pH on kinetics of binding of mRNA-cap analogs by translation initiation factor eIF4E , 2003, European Biophysics Journal.

[71]  A M Gronenborn,et al.  Disordered water within a hydrophobic protein cavity visualized by x-ray crystallography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[72]  B. McMahon,et al.  Electron transfer and protein dynamics in the photosynthetic reaction center. , 1998, Biophysical journal.

[73]  S. Rick,et al.  Hydration free energies and entropies for water in protein interiors. , 2004, Journal of the American Chemical Society.

[74]  B. Halle,et al.  Proton magnetic shielding tensor in liquid water. , 2002, Journal of the American Chemical Society.

[75]  R. Wade,et al.  Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam: a molecular dynamics study. , 1995, Biophysical journal.

[76]  H. Michel,et al.  Dynamic water networks in cytochrome C oxidase from Paracoccus denitrificans investigated by molecular dynamics simulations. , 2004, Biophysical journal.

[77]  T. Straatsma,et al.  THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS , 1987 .

[78]  Jeremy C. Smith,et al.  Low frequency enzyme dynamics as a function of temperature and hydration: A neutron scattering study , 2005 .

[79]  J Hermans,et al.  Hydrophilicity of cavities in proteins , 1996, Proteins.

[80]  Michael W. Mahoney,et al.  A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions , 2000 .

[81]  T. Straatsma,et al.  Internal Dynamics of Green Fluorescent Protein , 1999 .

[82]  D. Case,et al.  Generalized born models of macromolecular solvation effects. , 2000, Annual review of physical chemistry.

[83]  Jeremy C. Smith,et al.  Structural and energetic determinants of primary proton transfer in bacteriorhodopsin , 2006, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[84]  Dagmar Ringe,et al.  Solvent mobility and the protein 'glass' transition , 2000, Nature Structural Biology.

[85]  Rebecca C. Wade,et al.  COMPUTATIONAL ALCHEMY TO CALCULATE ABSOLUTE PROTEIN-LIGAND BINDING FREE ENERGY , 1998 .

[86]  An introduction to "Water in the cell": tamed Hydra? , 2001, Cellular and molecular biology.