Nucleic Acids Research Advance Access originally published online on August 4, 2009
Nucleic Acids Research 2009 37(17):5930-5942; doi:10.1093/nar/gkp618
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Nucleic Acids Research, 2009, Vol. 37, No. 17 5930-5942
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Differences in conformational dynamics of [Pt3(HPTAB)]6+–DNA adducts with various cross-linking modes
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China
*To whom correspondence should be addressed. Tel: +86 10 58805424; Fax: +86 10 58802075; Email: gjchen{at}bnu.edu.cn Correspondence may also be addressed to Yan Wang. Tel: +86 10 58805247; Fax: +86 10 58802075; Email: wangy{at}bnu.edu.cn
Received April 3, 2009. Revised July 8, 2009. Accepted July 9, 2009.
We present here molecular dynamics simulations and DNA conformational dynamics for a series of trinuclear platinum [Pt3(HPTAB)]6+-DNA adducts [HPTAB = N,N,N',N',N'',N''-hexakis (2-pyridyl-methyl)-1,3,5-tris(aminomethyl) benzene], including three types of bifunctional crosslinks and four types of trifunctional crosslinks. Our simulation results reveal that binding of the trinuclear platinum compound to a DNA duplex induces the duplex unwinding in the vicinity of the platination sites, and causes the DNA to bend toward the major groove. As a consequence, this produces a DNA molecule whose minor groove is more widened and shallow compared to that of an undamaged bare-DNA molecule. Notably, for trifunctional crosslinks, we have observed extensive DNA conformational distortions, which is rarely seen for normal platinum–DNA adducts. Our findings, in this study, thus provide further support for the idea that platinum compounds with trifunctional intra-strand or long-range-inter-strand cross-linking modes can generate larger DNA conformational distortions than other types of cross-linking modes.