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MD simulation of LNA-modified human telomeric G-quadruplexes: A free energy calculation
A.K. Chaubey, , R.P. Ojha
Published in Birkhauser Boston
2015
Volume: 24
   
Issue: 2
Pages: 753 - 763
Abstract
One of the principal tools in the theoretical study of biological molecules is the method of molecular dynamic simulation. MD simulations have provided detailed information on the fluctuation and conformation changes of the system. It offers the prospects of detailed description of the dynamical structure with ion and water at molecular level. In this work, we have taken an oligomeric part of human telomeric DNA, d(TAGGGT), to form a tetrameric quadruplex structure and generate four modified complexes. For modification, we have taken locked nucleic acid. Here, we report the relative stability of these modified structures under K+ ion conditions and binding interaction between the strands as determined by MD simulation followed by energy calculation. MM-PBSA method is performed for the determination of most stable complex. In free energy calculation, different strands are taken as the ligand and receptor. The energetic study shows that a modified quadruplex, in which first two modified strands are bind with other two unmodified strands, is more stable than other complexes. The formation and stabilization of these quadruplexes have been shown to inhibit the activity of telomerase, thus establishing telomeric quadruplex as an attractive target for cancer therapeutic intervention. © 2014 Springer Science+Business Media New York.
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Published in Birkhauser Boston
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