Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Nucleic Acids Research |
| MU Faculty or unit | |
| Citation | |
| Web | http://nar.oxfordjournals.org/content/41/4/2723.long |
| Doi | http://dx.doi.org/10.1093/nar/gks1331 |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; B-DNA; FORCE-FIELD; NUCLEIC-ACIDS; CENTER-DOT; SIMULATIONS; STABILITY; RNA; RECOGNITION |
| Attached files | |
| Description | The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. Although G-quartet stems have been well characterized, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 mu s. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A: A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology. |
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