Abstract
Previous time resolved measurements had indicated that protons could propagate on the surface of a protein, or a membrane, by a special mechanism that enhances the shuttle of the proton towards a specific site [1]. It was proposed that a proper location of residues on the surface contributes to the proton shuttling function. In the present study, this notion was further investigated using molecular dynamics, with only the mobile charge replaced by Na+ and Cl− ions. A molecular dynamics simulation of a small globular protein (the S6 of the bacterial ribosome) was carried out in the presence of explicit water molecules and four pairs of Na+ and Cl− ions. A 10 ns simulation indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. Yet it was noted that, close to some domains, the ions extended their duration near the surface, suggesting that the local electrostatic potential prevented them from diffusing to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed.
Similar content being viewed by others
References
Nachliel, E., Gutman, M., Tittor, J. and Oesterhelt, D.: Proton Transfer Dynamics on the Surface of the Late M State of Bacteriorhodopsin, Biophys. J. 83 (2002), 416–426.
Bizzarri, A.R. and Cannistraro, S.: Molecular Dynamics of Water at the Protein-Solvent Interface, J. Phys. Chem. B 106 (2002), 6617–6633.
Makarov, V., Pettitt, B.M. and Feig, M.: Solvation and Hydration of Proteins and Nucleic Acids: A Theoretical View of Simulation and Experiment, Acc. Chem. Res. 35 (2002), 376–384.
Svergun, D.I., Richard, S., Koch, M.H., Sayers, Z., Kuprin, S. and Zaccai, G.: Protein Hydration in Solution: Experimental Observation by X-ray and Neutron Scattering, Proc. Natl. Acad. Sci. U.S. A. 95 (1998), 2267–2272.
Smith, J.C., Merzel, F., Verma, C.S. and Fischer, S.: Protein Hydration Water: Structure and Thermodynamics, J. Mol. Liquid 101 (2002), 27–33.
Schiffer, C.A. and van Gunsteren, W.F.: Accessibility and Order of Water Sites in and Around Proteins: A Crystallographic Time-Averaging Study, Proteins 36 (1999), 501–511.
Sanschagrin, P.C. and Kuhn, L.A.: Cluster Analysis of Consensus Water Sites in Thrombin and Trypsin Shows Conservation Between Serine Proteases and Contributions to Ligand Specificity, Protein Sci. 7 (1998), 2054–2064.
Fenimore, P.W., Frauenfelder, H., McMahon, B.H. and Parak, F.G.: Slaving: Solvent Fluctuations Dominate Protein Dynamics and Functions, Proc. Natl. Acad. Sci. U.S.A. 99 (2002), 16047–16051.
Higo, J. and Nakasako, M.: Hydration Structure of Human Lysozyme Investigated by Molecular Dynamics Simulation and Cryogenic X-Ray Crystal Structure Analyses: On the Correlation Between Crystal Water Sites, Solvent Density, and Solvent Dipole, J. Comput. Chem. 23 (2002), 1323–1336.
Curtis, R.A., Prausnitz, J.M. and Blanch, H.W.: Protein-Protein and Protein-Salt Interactions in Aqueous Protein Solutions Containing Concentrated Electrolytes, Biotechnol. Bioeng. 57 (1998), 11–21.
Scheiner, S.: Quantum Chemical Studies of Proton Transport Through Biomembranes, Ann. N.Y. Acad. Sci. 367 (1981), 493–509.
Gutman, M., Huppert, D. and Nachliel, E.: Kinetic Studies of Proton Transfer in the Microenvironment of a Binding Site, Eur. J. Biochem. 121 (1982), 637–642.
Paddock, M.L., McPherson, P.H., Feher, G. and Okamura, M.Y.: Pathway of Proton Tranfer in Bacterial Reaction Centers: Replacement of Serinve-L22 by Alanine Inhibits Electron and Proton Transfers Associated with Reduction of Quinone to Dihydroquinone, Proc. Natl. Acad. Sci. U.S.A. 87 (1990), 6803–6807.
Bashford, D. and Gerwert, K.: Electrostatic Calculations of the pKa Values of Ionizable Groups in Bacteriorhodopsin, J. Mol. Biol. 224 (1992), 473–486.
Heberle, J., Riesle, J., Thiedemann, G., Oesterhelt, D. and Dencher, N.A.: Proton Migration Along the Membrane Surface and Retarded Surface to Bulk Transfer, Nature 370 (1994), 379–382.
McPherson, P.H., Schonfeld, M., Paddock, M.L., Okamura, M.Y. and Feher, G.: Protonation and Free Energy Changes Associated with Formation of QBH2 in Native and Glu-L212→Gln Mutant Reaction Centers from Rhodobacter Sphaeroides, Biochemistry 33 (1994), 1181–1193.
le Coutre, J. and Gerwert, K.: Kinetic Isotope Effects Reveal an Ice-Like and a Liquid-Phase-type Intramolecular Proton Transfer in Bacteriorhodopsin, FEBS Lett. 398 (1996), 333–336.
Gutman, M. and Nachliel, E.: Time Resolved Dynamics of Proton Transfer in Proteinous Systems, Annu. Rev. Phys. Chem. 48 (1997), 329–356.
Adelroth, P., Paddock, M.L., Sagle, L.B., Feher, G. and Okamura, M.Y.: Identification of the Proton Pathway in Bacterial Reaction Centers: Both Protons Associated with Reduction of QB to QBH2 Share a Common Entry Point, Proc. Natl. Acad. Sci. U.S.A. 97 (2000), 13086–13091.
Zscherp, C., Schlesinger, R. and Heberle, J.: Time-Resolved FT-IR Spectroscopic Investigation of the pH-Dependent Proton Transfer Reactions in the E194Q Mutant of Bacteriorhodopsin, Biochem. Biophys. Res. Commun. 283 (2001), 57–63.
Gutman, M., Nachliel, E., Mezer, A. and Noivirt, O.: Gauging of Local Micro-Environment at Protein Water Interface by Time-Resolved Single-Proton Transfer Reactions, Ann. Eur. Acad. Sci. 1 (2003), 75–107.
Nachliel, E. and Gutman, M.: Kinetic Analysis of Proton Transfer Between Reactants Adsorbed to the Same Micelle. The Effect of Proximity on the Rate Constants, Eur. J. Biochem. 143 (1984), 83–88.
Gutman, M., Nachliel, E., Bamberg, E. and Christensen, B.: Time-Resolved Protonation Dynamics of a Black Lipid Membrane Monitored by Capacitative Currents, Biochim. Biophys. Acta 905 (1987), 390–398.
Checover, S., Marantz, Y., Nachliel, E., Gutman, M., Pfeiffer, M., Tittor, J., Oesterhelt, D. and Dencher, N.A.: Dynamics of the Proton Transfer Reaction on the Cytoplasmic Surface of Bacteriorhodopsin, Biochemistry 40 (2001), 4281–4292.
Tran-Thi, T.H., Gustavsson, T., Prayer, C., Pommeret, S. and Hynes, J.T.: Primary Ultrafast Events Preceding the Photoinduced Proton Transfer from Pyranine to Water, Chem. Phys. Lett. 329 (2000), 421–430.
Forster, T. and Volker, S.: Kinetics of Proton Transfer Reaction Involving Hydroxypyrene-Trisulfonate in Aqueous Solution by Nanosecond Laser Absorption Spectroscopy, Chem. Phys. Lett. 34 (1975), 1–5.
Weller, A.: Excited State Proton Transfer, Prog. React. Kinet. 1 (1961), 198–214.
Gutman, M. and Huppert, D.: Rapid pH and deltamuH+ Jump by Short Laser Pulse, J. Biochem. Biophys. Methods 1 (1979), 9–19.
Checover, S., Nachliel, E., Dencher, N.A. and Gutman, M.: Mechanism of Proton Entry into the Cytoplasmic Section of the Proton-Conducting Channel of Bacteriorhodopsin, Biochemistry 36 (1997), 13919–13928.
Marantz, Y., Nachliel, E., Aagaard, A., Brzezinski, P. and Gutman, M.: The Proton Collecting Function of the Inner Surface of Cytochrome C Oxidase from Rhodobacter Sphaeroides, Proc. Natl. Acad. Sci. U.S.A. 95 (1998), 8590–8595.
Cohen, B. and Huppert, D.: Evidence for a Continuous Transition from Nonadiabatic to Adiabatic Proton Transfer Dynamics in Protic Solvents. J. Phys. Chem. A 105 (2001), 2980–2988.
Agalarov, S.C., Prasad, G.S., Funke, P.M., Stout, C.D. and Williamson, J.R.: Structure of the S15,S6,S18-rRNA Complex: Assembly of the 30S Ribosome Central Domain, Science 288 (2000), 107–112.
Lindahl, E., Hess, B. and van der Spoel, D.: Gromacs 3.0: A Package for Molecular Simulation and Trajectory Analysis, J. Mol. Med. 7 (2001), 306–317.
van Gunsteren, W.F. and Berendsen, H.J.C.: Gromos-87 Manual, Biomos BV, Groningen, 1987.
van Buuren, A.R., Marrink, S.J. and Berendsen, H.J.C.: A Molecular Dynamics Study of the Decane/Water Interface, J. Phys. Chem. 97 (1993), 9206–9212.
Mark, A.E., van Helden, S.P., Smith, P.E., Janssen, L.H.M. and van Gunsteren, W.F.: Convergence Properties of Free Energy Calculations: Alpha-Cyclodextrin Complexes as a Case Study, J. Am. Chem. Soc. 116 (1994), 6293–6302.
van Buuren, A.R. and Berendsen, H.J.C.: Molecular Dynamics Simulations of the Stability of a 22 Residue Alpha-Helix in Water and 30% Trifluoroethanol, Biopolymers 33 (1993), 1159–1166.
Liu, H., Muller-Plathe, F. and van Gunsteren, W.F.A.: Force Field for Liquid Dimethyl Sulfoxide and Liquid Proporties of Liquid Dimethyl Sulfoxide Calculated Using Molecular Dynamics Simulation, J. Am. Chem. Soc. 117 (1995), 4363–4366.
Lindahl, M., Svensson, L.A., Liljas, A., Sedelnikova, S.E., Eliseikina, I.A., Fomenkova, N.P., Nevskaya, N., Nikonov, S.V., Garber, M.B. and Muranova, T.A.: Crystal Structure of the Ribosomal Protein S6 from Thermus Thermophilus, EMBO J. 13 (1994), 1249–1254.
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E.: The Protein Data Bank, Nucleic Acids Res. 28 (2000), 235–242.
Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F. and Hermans, J.: Interaction Models for Water in Relation to Protein Hydration, Nature 224 (1969), 175–177.
van der Spoel, D. and Berendsen, H.J.C.: Molecular Dynamics Simulations of Leu-Enkephalin in Water and DMSO, Biophys. J. 72 (1997), 2032–2041.
Tieleman, D.P. and Berendsen, H.J.C.: Molecular Dynamics Simulations of a Fully Hydrated Dipalmitoylphosphatidylcholine Bilayer with Different Macroscopic Boundary Conditions and Parameters, J. Chem. Phys. 105 (1996), 4871–4880.
Hess, B., Bekker, H., Berendsen, H.J.C. and Fraaije, J.G.E.M.: LINCS: A Linear Constraint Solver for Molecular Simulations, J. Comp. Chem. 18 (1997), 1463–1472.
Miyamoto, S. and Kollman, P.A.: SETTLE: An Analytical Version of the SHAKE and RATTLE Algorithms for Rigid Water Models, J. Comp. Chem. 13 (1992), 952–962.
Berendsen, H.J.C., Postma, J.P.M., DiNola, A. and Haak, J.R.: Molecular Dynamics with Coupling to an External Bath, J. Chem. Phys. 81 (1984), 3684–3690.
Darden, T., York, D. and Pedersen, L.: Particle Mesh Ewald: An N-log(N) Method for Ewald Sums in Large Systems, J. Chem. Phys. 98 (1993), 10089–10092.
Baker, N.A., Sept, D., Joseph, S., Holst, M.J. and McCammon, J.A.: Electrostatics of Nanosystems: Application to Microtubules and the Ribosome, Proc. Natl. Acad. Sci. U.S.A. 98 (2001), 10037–10041.
Humphrey, W., Dalke, A. and Schulten, K.: VMD: Visual Molecular Dynamics, J. Mol. Gr. 14 (1996), 33–38.
van der Spoel, D., van Maaren, P.J. and Berendsen, H.J.C.: A Systematic Study of Water Models for Molecular Simulation: Derivation of Water Models Optimized for Use with a Reaction Field, J. Chem. Phys. 108 (1998), 10220–10230.
Harned, S.H. and Hildreth, C.L.: The Differential Diffusion Coefficients of Lithium and Sodium Chlorides in Dilute Aqueous Solution at 25 degrees. J. Am. Chem. Soc. 73 (1951), 650–652.
Stokes, R.H.: The Diffusion Coefficients of Eight Uni-Univalent Electrolytes in Aqueous Solution at 25, J. Am. Chem. Soc. 72 (1950), 2243–2247.
Macdonald, P.M. and Seelig, J.: Anion Binding to Neutral and Positively Charged Lipid Membranes, Biochemistry 27 (1988), 6769–6775.
Pandit, S.A., Bostic, D. and Berkowitz, M.L.: Molecular Dynamics Simulation of a Dipalmitoylphosphatidylcholine Bilayer with NaCl, Biophys. J. 84 (2003), 3743–3750.
Froloff, N., Windemuth, A. and Honig, B.: On the Calculation of Binding Free Energies Using Continuum Methods: Application to MHC Class I Protein-Peptide Interactions, Protein Sci. 6 (1997), 1293–1301.
Miyashita, O., Onuchic, J.N. and Okamura, M.Y.: Continuum Electrostatic Model for the Binding of Cytochrome c2 to the Photosynthesis Reaction Center from Rhodobacter Sphaeroides, Biochemistry 42 (2003), 11651–11660.
Marantz, Y., Einarsdottir, O.O., Nachliel, E. and Gutman, M.: Proton-Collecting Properties of Bovine Heart Cytochrome C Oxidase: Kinetic and Electrostatic Analysis, Biochemistry 40 (2001), 15086–15097.
Agmon, N.: The Grotthuss Mechanism, Chem. Phys. Lett. 244 (1995), 456–462.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Friedman, R., Nachliel, E. & Gutman, M. Protein Surface Dynamics: Interaction with Water and Small Solutes. J Biol Phys 31, 433–452 (2005). https://doi.org/10.1007/s10867-005-0171-2
Issue Date:
DOI: https://doi.org/10.1007/s10867-005-0171-2