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- Friedman, Ran, et al.
(författare)
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Minimum energy pathways for proton transfer between adjacent sites exposed to water
- 2007
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:21, s. 6059-6070
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Tidskriftsartikel (refereegranskat)abstract
- The capacity to transfer protons between surface groups is an innate property of many proteins. The transfer of a proton between donor and acceptor, located as far as 6−7 Å apart, necessitates the participation of water molecules in the process. In a previous study we investigated the mechanism of proton transfer (PT) between bulk exposed sites, a few ångströms apart, using as a model the proton exchange between the proton-binding sites of the fluorescein molecule in dilute aqueous solution.1 The present study expands the understanding of PT reactions between adjacent sites exposed to water through the calculation the minimum energy pathways (MEPs) by the conjugate peak refinement algorithm2 and a quantum-mechanical potential. The PT reaction trajectories were calculated for the fluorescein system with an increasing number of water molecules. The MEP calculations reveal that the transition state is highly strained and involves a supramolecular structure in which fluorescein and the interconnecting water molecules are covalently bonded together and the protons are shared between neighboring oxygens. These findings are in accord with the high activation energy, as measured for the reaction, and indicate that PT reactions on the surface proceed by a semi- or fully concerted rather than stepwise mechanism. A similar mechanism is assumed to be operative on the surface of proteins and renders water-mediated PT reactions as highly efficient as they are.
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| 2. |
- Friedman, Ran, et al.
(författare)
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Protein surface dynamics : Interaction with water and small solutes
- 2005
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Ingår i: Journal of biological physics (Print). - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 31:3, s. 433-452
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Friedman, Ran, et al.
(författare)
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The role of small intraprotein cavities in the catalytic cycle of bacteriorhodopsin
- 2003
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Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 85:2, s. 886-896
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Tidskriftsartikel (refereegranskat)abstract
- The last phase of the proton transfer cycle of bacteriorhodopsin calls for a passage of a proton from D38 to D96.This reaction utilizes a narrow shaft ;10-A˚ long that connects the two carboxylates that cross through a very hydrophobicdomain. As the shaft is too narrow to be permanently hydrated, there are two alternatives for the proton propagation into thechannel. The proton may propagate through the shaft without solvation at the expense of a high electrostatic barrier;alternatively, the shaft will expand to accommodate some water molecules, thus lowering the Born energy for the insertion ofthe charge into the protein (B. Scha¨ tzler, N. A. Dencher, J. Tittor, D. Oesterhelt, S. Yaniv-Checover, E. Nachliel, and G. Gutman,2003, Biophys. J. 84:671–686). A comparative study of nine published crystal-structures of bacteriorhodopsin identified, next tothe shaft, microcavities in the protein whose position and surrounding atoms are common to the reported structures. Some ofthe cavities either shrink or expand during the photocycle. It is argued that the plasticity of the cavities provides a working spaceneeded for the transient solvation of the shaft, thus reducing the activation energy necessary for the solvation of the shaft. Thissuggestion is corroborated by the recent observations of Klink et al. (B. U. Klink, R. Winter, M. Engelhard, and I. Chizhov, 2002,Biophys. J. 83:3490–3498) that the late phases of the photocycle (t $ 1 ms) are strongly inhibited by external pressure.
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