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Differences in conformational dynamics of [Pt₃(HPTAB)]⁶⁺-DNA adducts with various cross-linking modes

Zhu, Yanyan, Wang, Yan, Chen, Guangju
Nucleic acids research 2009 v.37 no.17 pp. 5930-5942
DNA, benzene, crosslinking, molecular dynamics, platinum
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.