Abstract
Molecular dynamics (MD) simulations based on a classical force field are increasingly being used to study the structure and dynamics of nucleic acids. Simulation studies are limited by the accuracy of the force field description and by the time scale accessible by current MD approaches. In the case of specific conformational transitions it is often possible to improve the sampling of possible states by adding a biasing or umbrella potential along some coordinate describing the conformational transition. It is also possible to extract the associated free energy change along the reaction coordinate. The development of advanced sampling methods such as the replica-exchange MD (REMD) approach allows significant enhancement of conformational sampling of nucleic acids. Recent applications of umbrella sampling and REMD simulation as well as combinations of both methodologies on nucleic acids will be presented. These approaches have the potential to tackle many open questions in structural biology such as the role of nucleic acid structure during recognition and packing and the function of nucleic acid fine structure and dynamics.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Affentranger, R., Tavernelli, I., & Di Iorio, E. E. (2006). A novel Hamiltonian replica exchange MD protocol to enhance protein conformational space sampling. Journal of Chemical Theory and Computation, 2, 217.
Al-Hashimi, H. M., & Walter, N. G. (2008). RNA dynamics: It is about time. Current Opinion in Structural Biology, 18, 321.
Babin, V., Baucom, J., Darden, T. A., & Sagui, C. (2006). Molecular dynamics simulations of DNA with polarizable force fields: Convergence of an ideal B-DNA structure to the crystallographic structure. The Journal of Physical Chemistry B, 110, 11571.
Barthel, A., & Zacharias, M. (2006). Conformational transitions in RNA single uridine and adenosine bulge structures: A molecular dynamics free energy simulation study. Biophysical Journal, 90, 2450.
Bowman, G. R., Huang, X., Yao, Y., Sun, J., Carlsson, G., et al. (2008). Structural insight into RNA hairpin folding intermediates. Journal ofthe American Chemical Society, 130, 9676
Cheatham, T. E. (2004). Simulation and modeling of nucleic acid structure, dynamics and interactions. Current Opinion in Structural Biology, 14, 360.
Chen, J., Dupradeau, F. Y., Case, D. A., Turner, C. J., & Stubbe, J. (2007). Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4′-oxidized abasic sites. Biochemistry, 46, 3096.
Cheng, X., & Blumenthal, R. M. (2008). Mammalian DNA methyltransferases: A structural perspective. Structure, 16, 341.
Cloutier, T. E., & Widom, J. (2004). Spontaneous sharp bending of double-stranded DNA. Molecular Cell, 14, 355.
Curuksu, J., & Zacharias, M. (2009). Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach. Journal of Chemical Physics, 130, 104110.
Curuksu, J., Zakrzewska, K., & Zacharias, M. (2008). Magnitude and direction of DNA bending induced by screw-axis orientation: Influence of sequence, mismatches and abasic sites. Nucleic Acids Research, 36, 2268.
Curuksu, J., Sponer, J., & Zacharias, M. (2009a). Elbow flexibility of the kt38 RNA kink-turn motif investigated by free-energy molecular dynamics simulations. Biophysical Journal, 97, 2004.
Curuksu, J., Zacharias, M., Lavery, R., & Zakrzewska, K. (2009b). Local and global effects of strong DNA bending induced during molecular dynamics simulations. Nucleic Acids Research, 37, 3766.
Dalhus, B., Laerdahl, J. K., Backe, P. H., & Bjoras, M. (2009). DNA base repair-recognition and initiation of catalysis. FEMS Microbiology Reviews, 33, 1044.
Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N â‹…log(N) method for Ewald sums in large systems. Search Results, Journal of Chemical Physics, 98, 10089.
DeJong, E. S., Luy, B., & Marino, J. P. (2002). RNA and RNA-protein complexes as targets for therapeutic intervention. Current Topics in Medicinal Chemistry, 2, 289.
Demple, B., & Harrison, L. (1994). Repair of oxidative damage to DNA: Enzymology and biology. Annual Review of Biochemistry, 63, 915.
Djuranovic, D., & Hartmann, B. (2004). DNA fine structure and dynamics in crystals and in solution: The impact of BI/BII backbone conformations. Biopolymers, 73, 356.
Foloppe, N., & MacKerell, A. D., Jr. (2000). All-atom empirical force field for nucleic acids: I. parameter optimization based on small molecule and condensed phase macromolecular target data. Journal of Computational Chemistry, 21, 86.
Fujimoto,H.,Pinak,M.,Nemoto,T.,O’Neill,P.,Kume,E.,Saito,K.,&Maekawa, H. (2005). Molecular dynamics simulation of clustered DNA damage sites containing8-oxoguanineandabasicsite.JournalofComputationalChemistry, 26, 788.
Fukunishi, H., Watanabe, O., & Takada, S. (2002). On the Hamiltonian replica exchange method for efficient sampling of biomolecular systems: Application to protein structure prediction. Journal of Chemical Physics, 116, 9058.
Furtig, B., Richter, C., Wöhnert, J., & Schwalbe, H. (2003). NMR spectroscopy of RNA. European Journal of Chemical Biology, 4, 936.
Garcia, H. G., Grayson, P., Han, L., Inamdar, M., Kondev, J., Nelson, P. C., Phillips, R., Widom, J., & Wiggins, P. A. (2007). Biological consequences of tightly bent DNA: The other life of a macromolecular celebrity. Biopolymers, 85, 115.
Garcia, A. E., & Paschek, D. (2008). Simulation of the pressure and temperature folding/unfolding equilibrium of a small RNA hairpin. Journal of the American Chemical Society, 130, 815.
Giudice, E., & Lavery, R. (2003). Nucleic acid base pair dynamics: The impact of sequence and structure using free-energy calculations. Journal of the American Chemical Society, 125, 4998.
Giudice, E., Várnai, P., & Lavery, R. (2003). Base pair opening within B-DNA: Free energy pathways for GC and AT pairs from umbrella sampling simulations. Nucleic Acids Research, 31, 1434.
Gnanakaran, S., Nymeyer, H., Portman, J., Sanbonmatsu, K. Y., & Garcia, A. E. (2003). Peptide folding simulations. Current Opinion in Structural Biology, 15, 168.
Hall, K. B. (2008). RNA in motion. Current Opinion in Chemical Biology, 12, 612.
Hart, K., Nyström, B., Öhman, M., & Nilsson, L. (2005). Molecular dynamics simulations and free energy calculation of base flipping in dsRNA. RNA, 11, 609.
Hashem, Y., & Auffinger, P. (2007). Nucleic solvation: From outside to insight. Current Opinion in Structural Biology, 17, 325.
Huang, N., Banavali, N. K., & MacKerell, A. D., Jr. (2003). Protein facilitated base flipping in DNA by cytosine-5-methyltranferase. Proceedings ofthe National Academy of Sciences of the United States of America, 100, 68.
Jang, S., Shin, S., & Pak, Y. (2003). Replica-exchange method using the generalized effective potential. Physical Review Letters, 91, 58305.
Kaihsu T. (2004). Conformational sampling for the impatient. Biophysical Chemistry, 107, 213.
Kannan, S., Kohlhoff, K., & Zacharias, M. (2006). B-DNA under stress: Over and un-twisting ofDNA during molecular dynamics simulations. Biophysical Journal, 91, 2956.
Kannan, S., & Zacharias, M. (2007a). Folding of a DNA Hairpin loop structure in explicit solvent using replica-exchange molecular dynamics simulations. Biophysical Journal, 93, 3218.
Kannan, S., & Zacharias, M. (2007b). Enhanced sampling of peptide and protein conformations using replica exchange simulations with a peptide backbone biasing-potential. Proteins, 66, 697.
Kannan, S., & Zacharias, M. (2009). Simulation of DNA double-strand dissociation and formation during replica-exchange molecular dynamics simulations. Physical Chemistry Chemical Physics, 11, 10589.
Kim, J. L., & Burley, S. K. (1994). 1.9Â Ã… resolution refined structure of TBP recognizing the minor groove of TATAAAAG. Nature Structural & Molecular Biology, 1, 638.
Kumar, S. D., Bouzida, R., Swendsen, H., Kollman, P. A., & Rosenberg, J. M. (1992). The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. Journal of Computational Chemistry, 13, 1011.
Lankas, F., Lavery, R., & Maddocks, J. H. (2006). Kinking occurs during molecular dynamics simulations of small DNA minicircles. Structure, 14, 1527.
Lavery, R., et al. (2009). Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps. Biophysical Journal, 87, 3799.
Leontis, N. B., & Westhof, E. (2003). Analysis of RNA motifs. Current Opinion in Structural Biology, 13, 300.
Liu, P., Kim, B., Friesner, R. A., & Berne, B. A. (2005). Replica exchange with solute tempering: A method for sampling biological systems in explicit water. Proceedings of the National Academy of Sciences, 102, 13749.
MacKerell, A. D., Jr., & Banavali, N. (2000). All-atom empirical force field for nucleic acids: II. Application to molecular dynamics simulations of DNA and RNA in solution. Journal of Computational Chemistry, 21, 105.
Mackerell, A. D., Jr., & Nilsson, L. (2008). Molecular dynamics simulations of nucleic acid-protein complexes. Current Opinion in Structural Biology, 18, 194.
McDowell, S. E, Spacková, N., Sponer, J., & Walter, N. G. (2007). Molecular dynamics simulations of RNA: An in silico single molecule approach. Biopolymers, 85, 169.
Moody, E. M., & Bevilacqua, P. C. (2003). Folding of a stable DNA motif involves a highly cooperative network of interactions. Journal of the American Chemical Society, 125, 16285.
Nikolov, D. B., Chen, H., Halay, E. D., Hoffman, A., Roeder, R. G., & Burley, S. K. (1996). Crystal structure of a Human TATA box-binding protein/TATA element complex. Proceedings of the National Academy of Sciences of the United States of America, 93, 4862.
Norberg, J., & Nilsson, L. (1995). Potential of mean force calculations of the stacking-unstacking process in single-stranded deoxyribodinucleoside monophosphates. Biophysical Journal, 69, 2277.
Ong, M. S., Richmond, T. J., & Davey, C. A. (2007). DNA stretching and extreme kinking in the nucleosome core. Journal of Molecular Biology, 368, 1067.
Orozco, M., Noy, A., & Pérez, A. (2008). Recent advances in the study of nucleic acid flexibility by molecular dynamics. Current Opinion in Structural Biology, 18, 185.
Perez, A., Marchan, I., Svozil, D., Sponer, J., Cheatham, T. E., III, Laughton, C. A., & Orozco. M. (2007a). Refinement of the AMBER force field for nucleic acids: Improving the description of/conformers. Biophysical Journal, 92, 3817.
Perez, A., Luque, F. J., & Orozco, M. (2007b). Dynamics of B-DNA on the microsecond time scale. Journal of the American Chemical Society, 129, 14739–14745
Portella, G., & Orozco, M. (2010). Multiple routes to characterize the folding of a small DNA Hairpin. Angewandte Chemie International Edition England, 49, 7673–7676.
Sanbonmatsu, K. Y., & Tung, C. S. (2007). High performance computing in biology: Multimillion atom simulations of nanoscale systems. Journal of Structural Biology, 157, 470.
Shroff, H., Reinhard, B. M., Siu, M., Agarwal, H., Spakowitz, A., & Liphardt, J. (2005). Biocompatible force sensor with optical readout and dimensions of 6nm. Nano Letters, 5, 1509.
Steitz, T. A. (2008). A structural understanding of the dynamic ribosome machine. Nature Reviews Molecular Cell Biology, 9, 242.
Sugita, Y., & Okamoto, Y. (1999). Replica-exchange molecular dynamics method for protein folding. Chemical Physics Letters, 314, 141.
Sugita Y., Kitao, A., & Okamoto, Y. (2000). Multidimensional replica-exchange method for free energy calculations. Journal of Chemical Physics, 113, 6042.
Swendsen, R. H., & Wang, J. S. (1986). Replica Monte Carlo simulations of spin glasses. Physical Review Letters, 57, 2607.
Travers, A., & Muskhelishvili, G. (2005). Bacterial chromatin. Current Opinion in Genetics & Development, 15, 507
Varnai, P., Djuranovic, D., Lavery, R., & Hartmann, B. (2002). alpha/gamma Transitions in the B-DNA backbone. Nucleic Acids Research, 30, 5398.
Villa, A., Widjajakusuma, E., & Stock, G. (2008). Molecular dynamics simulation of the structure, dynamics, and thermostability of the RNA Hairpins uCACGg and cUUCGg. The Journal ofPhysical Chemistry B, 112, 134.
Wiggins, P. A., Van Der Heijden, T., Moreno-Herrero, F., Spakowitz, A., Phillips, R., Widom, J., Ceekers, C., & Nelson, P. C. (2006). High flexibility of DNA on short length scales probed by atomic force microscopy. Nature Nanotechnology, 1, 137.
Wong, H. M., Payet, L., & Huppert, J. L. (2009). Function and targeting of G-quadruplexes. Current Opinion in Molecular Therapeutics, 11, 146.
Yoshizawa, S., Kawai, G., Watanabe, K., Miura, K., & Hirao, I. (1997). GNA trinucleotide loop sequences producing extraordinarily stable DNA minihairpins. Biochemistry, 36, 4761.
Yuan, C., Chen, H., Lou, X. W., & Archer, L. A. (2008). DNA bending stiffness on small length scales. Physical Review Letters, 100, 018102.
Zacharias, M. (2000). Simulation of the structure and dynamics of nonhelical RNA motifs. Current Opinion in Structural Biology, 10, 307.
Zacharias, M. (2003). Perspectives of drug design that targets RNA. Current Medicinal Chemistry, 2, 161.
Zacharias, M. (2006). Minor groove deformability of DNA: A molecular dynamics free energy simulation study. Biophysical Journal, 91, 882.
Zacharias, M. (2008). Combining elastic network analysis and molecular dynamics simulations by Hamiltonian replica exchange. Journal of Chemical Theory and Computation, 4, 477.
Zakrzewska, K. (2003). DNA deformation energetics and protein binding. Biopolymers, 70, 414.
Zhuang, Z., Jaeger, L., & Shea, J. E. (2007). Probing the structural hierarchy and energy landscape of an RNA T-loop Hairpin. Nucleic Acids Research, 35, 6995.
Acknowledgments
This work was supported by a grant (I/80485) from the Volkswagen Foundation to M.Z.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this entry
Cite this entry
Curuksu, J., Kannan, S., Zacharias, M. (2012). Molecular Dynamics and Advanced Sampling Simulations of Nucleic Acids. In: Leszczynski, J. (eds) Handbook of Computational Chemistry. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0711-5_32
Download citation
DOI: https://doi.org/10.1007/978-94-007-0711-5_32
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0710-8
Online ISBN: 978-94-007-0711-5
eBook Packages: Chemistry and Materials ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics