Raghunathan G, Kieber-Emmons T, Rein R, Alderfer J L
Department of Biophysics, Roswell Park Memorial Institute, Buffalo, NY 14263.
J Biomol Struct Dyn. 1990 Feb;7(4):899-913. doi: 10.1080/07391102.1990.10508531.
In an effort to understand the conformational and structural changes in DNA brought about by thymine photodimer, computer modeling and molecular mechanics energy calculations were performed on DNA hexamer and dodecamer duplexes containing a cis-syn photodimer. The conformation of the crystal structure of the cyanoethyl phosphate ester of the thymine dimer (Hruska et al., Biopolymers 25, 1399-1417 (1986)) was used in modeling the photodimer portion. Various starting conformations were used in the modeling procedure and the structures were minimized both retaining and later relaxing the crystallographic geometry of the cyclobutane ring. The results indicate that most of the deformation is restricted to the thymine dimer region, and that the conformational changes decrease rapidly on either side of the region containing the photodimer. The structural changes brought about by the introduction of the photodimer can be accommodated within six base paired duplex without significant bend in the DNA. More conformational changes are observed on the 5'-side of the photodimer than on the 3'-side. The conformational features, such as backbone torsion angles and sugar puckers, of the energy minimized structures are discussed in the context of the solution structures determined by NMR on a series of oligomers containing photodimers (Rycyna et al., Biochemistry 27, 3152-3163 (1988)).
为了了解胸腺嘧啶光二聚体引起的DNA构象和结构变化，对含有顺式-顺式光二聚体的DNA六聚体和十二聚体双链体进行了计算机建模和分子力学能量计算。胸腺嘧啶二聚体的氰基乙基磷酸酯晶体结构（赫鲁斯卡等人，《生物聚合物》25，1399 - 1417（1986））的构象用于对光二聚体部分进行建模。在建模过程中使用了各种起始构象，并且在保留和随后放松环丁烷环的晶体学几何结构的情况下对结构进行了最小化处理。结果表明，大部分变形局限于胸腺嘧啶二聚体区域，并且在包含光二聚体的区域两侧，构象变化迅速减小。光二聚体的引入所带来的结构变化可以在六个碱基对的双链体内得到容纳，而DNA不会有明显的弯曲。在光二聚体的5'侧比3'侧观察到更多的构象变化。在由含有光二聚体的一系列寡聚物的核磁共振确定的溶液结构的背景下，讨论了能量最小化结构的构象特征，如主链扭转角和糖环构象（里西纳等人，《生物化学》27，3152 - 3163（1988））。
