Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale
Data(s) |
01/02/2013
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Resumo |
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. While G-quartet stems have been well characterised, 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 µs. 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. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/closedAccess |
Fonte |
Islam , B , Sgobba , M , Laughton , C , Orozco , M , Sponer , J , Neidle , S , Haider , S & Shozeb Haider 2013 , ' Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale ' Nucleic Acids Research , vol 41 , no. 4 , pp. 2723 . DOI: 10.1093/nar/gks1331 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1300/1311 #Genetics |
Tipo |
article |