Foloppe N, Nilsson L, MacKerell A D
Center for Structural Biology, Department of Bioscience, Karolinska Institutet, S-141 57, Huddinge, Sweden.
Biopolymers. 2001;61(1):61-76. doi: 10.1002/1097-0282(2001)61:1<61::AID-BIP10047>3.0.CO;2-1.
In recent years, the use of high-level ab initio calculations has allowed for the intrinsic conformational properties of nucleic acid building blocks to be revisited. This has provided new insights into the intrinsic conformational energetics of these compounds and its relationship to nucleic acids structure and dynamics. In this article we review recent developments and present new results. New data include comparison of various levels of theory on conformational properties of nucleic acid building blocks, calculations on the abasic sugar, known to occur in vivo in DNA, on the TA conformation of DNA observed in the complex with the TATA box binding protein, and on inosine. Tests of the Hartree-Fock (HF), second-order Møller-Plesset (MP2), and Density Functional Theory/Becke3, Lee, Yang and Par (DFT/B3LYP) levels of theory show the overall shape of backbone torsional energy profiles (for gamma, epsilon, and chi) to be similar for the different levels, though some systematic differences are identified between the MP2 and DFT/B3LYP profiles. The east pseudorotation energy barrier in deoxyribonucleosides is also sensitive to the level of theory, with the HF and DFT/B3LYP east barriers being significantly lower (approximately 2.5 kcal/mol) than the MP2 counterpart (approximately 4.0 kcal/mol). Additional calculations at various levels of theory suggest that the east barrier in deoxyribonucleosides is between 3.0 and 4.0 kcal/mol. In the abasic sugar, the west pseudorotation energy barrier is found to be slightly lower than the east barrier and the south pucker is favored more than in standard nucleosides. Results on the TA conformation suggest that, at the nucleoside level, this conformation is significantly destabilized relative to the global energy minimum, or relative to the A- and B-DNA conformations. Deoxyribocytosine would destabilize the TA conformation more than other bases relative to the A-DNA conformation, but not relative to the B-DNA conformation.
近年来，高水平的从头算计算使得人们能够重新审视核酸构建单元的固有构象性质。这为这些化合物的固有构象能量学及其与核酸结构和动力学的关系提供了新的见解。在本文中，我们回顾了近期的进展并展示了新的结果。新数据包括对核酸构建单元构象性质的不同理论水平的比较、对无碱基糖（已知在体内DNA中出现）的计算、对与TATA盒结合蛋白复合物中观察到的DNA的TA构象的计算以及对次黄苷的计算。对Hartree-Fock（HF）、二阶Møller-Plesset（MP2）和密度泛函理论/Becke3、Lee、Yang和Par（DFT/B3LYP）理论水平的测试表明，对于不同水平，主链扭转能轮廓（对于γ、ε和χ）的整体形状相似，尽管在MP2和DFT/B3LYP轮廓之间发现了一些系统差异。脱氧核苷中的东假旋转能垒也对理论水平敏感，HF和DFT/B3LYP的东能垒明显低于MP2对应的能垒（约2.5千卡/摩尔），而MP2的能垒约为4.0千卡/摩尔。在不同理论水平上的额外计算表明，脱氧核苷中的东能垒在3.0至4.0千卡/摩尔之间。在无碱基糖中，发现西假旋转能垒略低于东能垒，并且南皱折比在标准核苷中更受青睐。关于TA构象的结果表明，在核苷水平上，相对于全局能量最小值或相对于A-和B-DNA构象，这种构象显著不稳定。相对于A-DNA构象，脱氧胞嘧啶比其他碱基更能使TA构象不稳定，但相对于B-DNA构象则不然。
