Abstract
One of the truly challenging problems for molecular dynamics (MD) simulations is demonstrating that the trajectories can sample not only in the vicinity of an experimentally determined structure, but also that the trajectories can find the correct experimental structure starting from some other structure. Frequently these transitions to the correct structure require that the simulations overcome energetic barriers to conformational change. Here we present unrestrained molecular dynamics simulations of the DNA analogs of the RNA 5'-GGACUUCGGUCC-3' hairpin tetraloop. In one simulation we have used deoxyuracil residues, and in the other we have used the native DNA deoxythymine residues. We demonstrate that, on a nanosecond time scale, MD is able to simulate the transitions of both of the A-DNA stems to B-DNA stems within the constraints imposed by the four-base loop that caps the helix. These results suggest that we are now in a position to use MD to address the nature of sequence-dependent structural effects in nonduplex DNA structures.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allain F. H., Varani G. Structure of the P1 helix from group I self-splicing introns. J Mol Biol. 1995 Jul 14;250(3):333–353. doi: 10.1006/jmbi.1995.0381. [DOI] [PubMed] [Google Scholar]
- Cheatham T. E., 3rd, Kollman P. A. Observation of the A-DNA to B-DNA transition during unrestrained molecular dynamics in aqueous solution. J Mol Biol. 1996 Jun 14;259(3):434–444. doi: 10.1006/jmbi.1996.0330. [DOI] [PubMed] [Google Scholar]
- Dickerson R. E., Goodsell D. S., Kopka M. L., Pjura P. E. The effect of crystal packing on oligonucleotide double helix structure. J Biomol Struct Dyn. 1987 Dec;5(3):557–579. doi: 10.1080/07391102.1987.10506413. [DOI] [PubMed] [Google Scholar]
- Dickerson R. E., Goodsell D. S., Neidle S. "...the tyranny of the lattice...". Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3579–3583. doi: 10.1073/pnas.91.9.3579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- James J. K., Tinoco I., Jr The solution structure of a d[C(TTCG)G] DNA hairpin and comparison to the unusually stable RNA analogue. Nucleic Acids Res. 1993 Jul 11;21(14):3287–3293. doi: 10.1093/nar/21.14.3287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipanov A., Kopka M. L., Kaczor-Grzeskowiak M., Quintana J., Dickerson R. E. Structure of the B-DNA decamer C-C-A-A-C-I-T-T-G-G in two different space groups: conformational flexibility of B-DNA. Biochemistry. 1993 Feb 9;32(5):1373–1389. doi: 10.1021/bi00056a024. [DOI] [PubMed] [Google Scholar]
- Ravishanker G., Swaminathan S., Beveridge D. L., Lavery R., Sklenar H. Conformational and helicoidal analysis of 30 PS of molecular dynamics on the d(CGCGAATTCGCG) double helix: "curves", dials and windows. J Biomol Struct Dyn. 1989 Feb;6(4):669–699. doi: 10.1080/07391102.1989.10507729. [DOI] [PubMed] [Google Scholar]
- Sakata T., Hiroaki H., Oda Y., Tanaka T., Ikehara M., Uesugi S. Studies on the structure and stabilizing factor of the CUUCGG hairpin RNA using chemically synthesized oligonucleotides. Nucleic Acids Res. 1990 Jul 11;18(13):3831–3839. doi: 10.1093/nar/18.13.3831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmitz U., James T. L. How to generate accurate solution structures of double-helical nucleic acid fragments using nuclear magnetic resonance and restrained molecular dynamics. Methods Enzymol. 1995;261:3–44. doi: 10.1016/s0076-6879(95)61003-0. [DOI] [PubMed] [Google Scholar]
- Schultz S. C., Shields G. C., Steitz T. A. Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees. Science. 1991 Aug 30;253(5023):1001–1007. doi: 10.1126/science.1653449. [DOI] [PubMed] [Google Scholar]
- Ulyanov N. B., James T. L. Statistical analysis of DNA duplex structural features. Methods Enzymol. 1995;261:90–120. doi: 10.1016/s0076-6879(95)61006-5. [DOI] [PubMed] [Google Scholar]
- Varani G., Cheong C., Tinoco I., Jr Structure of an unusually stable RNA hairpin. Biochemistry. 1991 Apr 2;30(13):3280–3289. doi: 10.1021/bi00227a016. [DOI] [PubMed] [Google Scholar]