Ha Duong T, Zakrzewska K
Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique, Paris, France.
J Biomol Struct Dyn. 1997 Jun;14(6):691-701. doi: 10.1080/07391102.1997.10508172.
DNA-drug complexes are important because of their pharmacological interest but, in addition, they provide a useful model to study the essential aspects of DNA recognition processes. In order to investigate the influence of ligand binding on the dynamic properties of DNA we have carried out normal mode analysis for complexes with drugs of two types: a typical intercalator, 9-aminoacridine, and a typical groove binder, netropsin. Normal modes are analysed in terms of helicoidal parameter variations with special attention being paid to global deformations of the double helix. The results show that the influence of these two drugs is very different. Intercalation of 9-aminoacridine leads to an increase in the flexibility of the intercalated dinucleotide step, with notably larger vibrational amplitudes for both roll and twist parameters compared to free DNA. In contrast, the groove binding of netropsin induces a stiffening of the DNA segment which is in contact with the drug reflected by decreased vibrational amplitudes for backbone angles and inter base pair helicoidal parameters and an increase in vibrations for adjacent base pairs in terms of buckle and propeller twist.
DNA-药物复合物因其药理学意义而备受关注，此外，它们还为研究DNA识别过程的基本方面提供了一个有用的模型。为了研究配体结合对DNA动态特性的影响，我们对与两种类型药物形成的复合物进行了简正模式分析：一种典型的嵌入剂9-氨基吖啶和一种典型的沟结合剂纺锤菌素。根据螺旋参数变化对简正模式进行分析，并特别关注双螺旋的整体变形。结果表明，这两种药物的影响非常不同。9-氨基吖啶的嵌入导致嵌入的二核苷酸步灵活性增加，与游离DNA相比，滚动和扭转参数的振动幅度明显更大。相比之下，纺锤菌素的沟结合导致与药物接触的DNA片段变硬，这表现为主链角度和碱基对间螺旋参数的振动幅度降低，以及相邻碱基对在弯曲和螺旋桨扭转方面的振动增加。
