Abstract
Hydration sites are high-density regions in the three-dimensional time-averaged solvent structure in molecular dynamics simulations and diffraction experiments. In a simulation of sperm whale myoglobin, we found 294 such high-density regions. Their positions appear to agree reasonably well with the distributions of waters of hydration found in 38 x-ray and 1 neutron high-resolution structures of this protein. The hydration sites are characterized by an average occupancy and a combination of residence time parameters designed to approximate a distribution of residence times. It appears that although the occupancy and residence times of the majority of sites are rather bulk-like, the residence time distribution is shifted toward the longer components, relative to bulk. The sites with particularly long residence times are located only in the cavities and clefts of the protein. This indicates that other factors, such as hydrogen bonds and hydrophobicity of underlying protein residues, play a lesser role in determining the residence times of the longest-lived sites.
Full Text
The Full Text of this article is available as a PDF (696.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abseher R., Schreiber H., Steinhauser O. The influence of a protein on water dynamics in its vicinity investigated by molecular dynamics simulation. Proteins. 1996 Jul;25(3):366–378. doi: 10.1002/(SICI)1097-0134(199607)25:3<366::AID-PROT8>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
- Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
- Brunne R. M., Liepinsh E., Otting G., Wüthrich K., van Gunsteren W. F. Hydration of proteins. A comparison of experimental residence times of water molecules solvating the bovine pancreatic trypsin inhibitor with theoretical model calculations. J Mol Biol. 1993 Jun 20;231(4):1040–1048. doi: 10.1006/jmbi.1993.1350. [DOI] [PubMed] [Google Scholar]
- Burling F. T., Weis W. I., Flaherty K. M., Brünger A. T. Direct observation of protein solvation and discrete disorder with experimental crystallographic phases. Science. 1996 Jan 5;271(5245):72–77. doi: 10.1126/science.271.5245.72. [DOI] [PubMed] [Google Scholar]
- Denisov V. P., Halle B. Protein hydration dynamics in aqueous solution. Faraday Discuss. 1996;(103):227–244. doi: 10.1039/fd9960300227. [DOI] [PubMed] [Google Scholar]
- Gu W., Schoenborn B. P. Molecular dynamics simulation of hydration in myoglobin. Proteins. 1995 May;22(1):20–26. doi: 10.1002/prot.340220104. [DOI] [PubMed] [Google Scholar]
- Hummer G., García A. E., Soumpasis D. M. Hydration of nucleic acid fragments: comparison of theory and experiment for high-resolution crystal structures of RNA, DNA, and DNA-drug complexes. Biophys J. 1995 May;68(5):1639–1652. doi: 10.1016/S0006-3495(95)80381-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kovacs H., Mark A. E., van Gunsteren W. F. Solvent structure at a hydrophobic protein surface. Proteins. 1997 Mar;27(3):395–404. doi: 10.1002/(sici)1097-0134(199703)27:3<395::aid-prot7>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- Lounnas V., Pettitt B. M. A connected-cluster of hydration around myoglobin: correlation between molecular dynamics simulations and experiment. Proteins. 1994 Feb;18(2):133–147. doi: 10.1002/prot.340180206. [DOI] [PubMed] [Google Scholar]
- Lounnas V., Pettitt B. M. Distribution function implied dynamics versus residence times and correlations: solvation shells of myoglobin. Proteins. 1994 Feb;18(2):148–160. doi: 10.1002/prot.340180207. [DOI] [PubMed] [Google Scholar]
- Makarov V. A., Andrews B. K., Pettitt B. M. Reconstructing the protein-water interface. Biopolymers. 1998 Jun;45(7):469–478. doi: 10.1002/(SICI)1097-0282(199806)45:7<469::AID-BIP1>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
- Makarov V. A., Feig M., Andrews B. K., Pettitt B. M. Diffusion of solvent around biomolecular solutes: a molecular dynamics simulation study. Biophys J. 1998 Jul;75(1):150–158. doi: 10.1016/S0006-3495(98)77502-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips G. N., Jr, Pettitt B. M. Structure and dynamics of the water around myoglobin. Protein Sci. 1995 Feb;4(2):149–158. doi: 10.1002/pro.5560040202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quillin M. L., Arduini R. M., Olson J. S., Phillips G. N., Jr High-resolution crystal structures of distal histidine mutants of sperm whale myoglobin. J Mol Biol. 1993 Nov 5;234(1):140–155. doi: 10.1006/jmbi.1993.1569. [DOI] [PubMed] [Google Scholar]
- Rudnicki W. R., Pettitt B. M. Modeling the DNA-solvent interface. Biopolymers. 1997 Jan;41(1):107–119. doi: 10.1002/(SICI)1097-0282(199701)41:1<107::AID-BIP10>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
- Scanlon W. J., Eisenberg D. Solvation of crystalline proteins: theory and its application to available data. J Mol Biol. 1975 Nov 5;98(3):485–502. doi: 10.1016/s0022-2836(75)80082-9. [DOI] [PubMed] [Google Scholar]
- Schoenborn B. P., Garcia A., Knott R. Hydration in protein crystallography. Prog Biophys Mol Biol. 1995;64(2-3):105–119. doi: 10.1016/0079-6107(95)00012-7. [DOI] [PubMed] [Google Scholar]
- Teeter M. M. Water-protein interactions: theory and experiment. Annu Rev Biophys Biophys Chem. 1991;20:577–600. doi: 10.1146/annurev.bb.20.060191.003045. [DOI] [PubMed] [Google Scholar]
- Tilton R. F., Jr, Kuntz I. D., Jr, Petsko G. A. Cavities in proteins: structure of a metmyoglobin-xenon complex solved to 1.9 A. Biochemistry. 1984 Jun 19;23(13):2849–2857. doi: 10.1021/bi00308a002. [DOI] [PubMed] [Google Scholar]