CONFORMATIONAL FLEXIBILITY OF NUCLEOSOMES: A MOLECULAR DYNAMICS STUDY
Abstract
One of the major problems of molecular biology is studying the underlying principles of chromatin work. This problem is associated with understanding the processes of epigenetic regulation of gene expression, DNA repair and heredity mechanisms. The basic unit of chromatin organization is nucleosome, which consists of DNA and histone proteins. For a long time nucleosome structure obtained by X-ray crystallography was considered as the ultimate and main conformational state of nucleosomes, but recent experimental data indicates that chromatin functions depends on conformation state of nucleosomes. Nevertheless, there is no detailed understanding of the conformational dynamics of nucleosomes at the atomistic level. In this paper, we have addressed this problem using molecular dynamics simulations of nucleosome in explicit solvent. We have investigated the dynamics of nucleosome on the 500 ns time interval, produced covariance analysis of the trajectory and derived the collective motions, studied the distribution of water molecules in the system and assumed the role of internal water.
About the Authors
G. A. Armeev
биологический факультет МГУ
Russian Federation
Russian Federation
K. V. Shaitan
биологический факультет МГУ
Russian Federation
Russian Federation
A. K. Shaytan
биологический факультет МГУ
Russian Federation
Russian Federation
References
1. Kornberg R.D. Chromatin structure: A repeating unit of histones and DNA // Science. 1974. Vol. 184. N 4139. P. 868—871.
2. Luger K., Mader A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 А a resolution // Nature. 1997. Vol. 389. N 6648. P. 251—260.
3. Talbert P.B., Ahmad K., Almouzni G. A unified phylogeny-based nomenclature for histone variants // Epigenet. Chromatin. 2012. Vol. 5. N 1. P. 7.
4. Burgess R.J., Zhang Z. Histone chaperones in nucleosome assembly and human disease // Nat. Struct. Mol. Biol. 2013. Vol. 20. N 1. P. 14—22.
5. Biswas M., Langowski J., Bishop T.C. Atomistic simulations of nucleosomes // Wiley Interdiscip Rev. Comput. Mol. Sci. 2013. Vol. 3. N 4. P. 378—392.
6. Zlatanova J., Bishop T.C., Victor J.M., Jackson V., van Holde K. The nucleosome family: Dynamic and growing // Structure. 2009. Vol. 17. N 2. P. 160—171.
7. Tomschik M., van Holde K., Zlatanova J. Nucleosome dynamics as studied by single-pair fluorescence resonance energy transfer: A reevaluation // J. Fluoresc. 2009. Vol. 19. N 1. P. 53—62.
8. Hondele M., Ladurner A.G. Catch me if you can how the histone chaperone fact capitalizes on nucleosome breathing // Nucleus-Austin. 2013. Vol. 4. N 6. P. 443—449.
9. Mozziconacci J., Victor J.M. Nucleosome gaping supports a functional structure for the 30 nm chromatin fiber // J. Struct. Biol. 2003. Vol. 143. N 1. P. 72—76.
10. Studitsky V.M., Clark D.J., Felsenfeld G. Overcoming a nucleosomal barrier to transcription // Cell. 1995. Vol. 83. N 1. P. 19—27.
11. Flaus A., Rencurel C., Ferreira H., Wiechens N., Owen-Hughes T. Sin mutations alter inherent nucleosome mobility // EMBO J. 2004. Vol. 23. N 2. P. 343—353.
12. Dror R.O., Dirks R.M., Grossman J.P., Xu H.F., Shaw D.E. Biomolecular simulation: A computational microscope for molecular biology // Annu. Rev. Biophys. 2012. Vol. 41. P. 429—452.
13. Lindorff-Larsen K., Piana S., Palmo K., Maragakis P., Klepeis J.L., Dror R.O., Shaw D.E. Improved sidechain torsion potentials for the amber ff99sb protein force field // Proteins. 2010. Vol. 78. N 8. P. 1950—1958.
14. Guy A.T., Piggot T.J., Khalid S. Single-stranded DNA within nanopores: Conformational dynamics and implications for sequencing; a molecular dynamics simulation study // Biophys. J. 2012. Vol. 103. N 5. P. 1028—1036.
15. Davey C.A., Sargent D.F., Luger K., Maeder A.W., Richmond T.J. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 А resolution // J. Mol. Biol. 2002. Vol. 319. N 5. P. 1097—1113.
16. Banks D.D., Gloss L.M. Equilibrium folding of the core histones: The H3-H4 tetramer is less stable than the H2A-H2B dimer // Biochemistry. 2003. Vol. 42. N 22. P. 6827—6839.
17. Essmann U., Perera L., Berkowitz M.L., Darden T., Lee H., Pedersen L.G. A smooth particle mesh ewald method // J. Chem. Phys. 1995. Vol. 103. N 19. P. 8577—8593.
18. Bussi G., Donadio D., Parrinello M. Canonical sampling through velocity rescaling // J. Chem. Phys. 2007. Vol. 126. N 1. P. 014101
19. Nose S., Klein M.L. Constant pressure moleculardynamics for molecular-systems // Mol. Phys. 1983. Vol. 50. N 5. P. 1055—1076.
20. Pronk S., Pall S., Schulz R., Larsson P., Bjelkmar P., Apostolov R., Shirts M.R., Smith J.C., Kasson P.M., van der Spoel D., Hess B., Lindahl E. Gromacs 4.5: A high-throughput and highly parallel open source molecular simulation toolkit // Bioinformatics. 2013. Vol. 29. N 7. P. 845—854.
21. Sadovnichy V., Tikhonravov A., Voevodin V., Opanasenko V. “Lomonosov”: Supercomputing at Moscow State University // Contemporary high performance computing: from petascale toward exascale / Ed. by S.V. Jeffery. Boca Raton: CRC Press, 2013. P. 283—307.
22. Humphrey W., Dalke A., Schulten K. Vmd: Visual molecular dynamics // J. Mol. Graph. Model. 1996. Vol. 14. N 1. P. 33—38.
23. Shaw D.E. Millisecond-long molecular dynamics simulations of proteins on a special-purpose machine // Biophys. J. 2013. Vol. 104. N 2. P. 45a.
Review
For citations:
Armeev G.A., Shaitan K.V., Shaytan A.K. CONFORMATIONAL FLEXIBILITY OF NUCLEOSOMES: A MOLECULAR DYNAMICS STUDY. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2015;(3):49-54. (In Russ.)
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