Zhu Yanyan, Wang Yan, Chen Guangju
College of Chemistry, Beijing Normal University, Beijing 100875, P R China.
Nucleic Acids Res. 2009 Sep;37(17):5930-42. doi: 10.1093/nar/gkp618. Epub 2009 Aug 4.
We present here molecular dynamics simulations and DNA conformational dynamics for a series of trinuclear platinum Pt(3)(HPTAB)-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.
我们在此展示了一系列三核铂Pt(3)(HPTAB) - DNA加合物[HPTAB = N,N,N',N',N'',N'' - 六(2 - 吡啶基 - 甲基)-1,3,5 - 三(氨甲基)苯]的分子动力学模拟和DNA构象动力学，包括三种双功能交联和四种三功能交联。我们的模拟结果表明，三核铂化合物与DNA双链的结合会在铂化位点附近诱导双链解旋，并使DNA向大沟弯曲。因此，这产生了一个与未受损裸DNA分子相比小沟更宽且浅的DNA分子。值得注意的是，对于三功能交联，我们观察到了广泛的DNA构象扭曲，这在正常的铂 - DNA加合物中很少见。因此，我们在本研究中的发现进一步支持了这样一种观点，即具有三功能链内或长程链间交联模式的铂化合物比其他类型的交联模式能产生更大的DNA构象扭曲。
