Kubar Tomás, Hanus Michal, Ryjácek Filip, Hobza Pavel
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.
Chemistry. 2005 Dec 16;12(1):280-90. doi: 10.1002/chem.200500725.
Correlated ab initio as well as semiempirical quantum chemical calculations and molecular dynamics simulations were used to study the intercalation of cationic ethidium, cationic 5-ethyl-6-phenylphenanthridinium and uncharged 3,8-diamino-6-phenylphenanthridine to DNA. The stabilization energy of the cationic intercalators is considerably larger than that of the uncharged one. The dominant energy contribution with all intercalators is represented by dispersion energy. In the case of the cationic intercalators, the electrostatic and charge-transfer terms are also important. The DeltaG of ethidium intercalation to DNA was estimated at -4.5 kcal mol(-1) and this value agrees well with the experimental result. Of six contributions to the final free energy, the interaction energy value is crucial. The intercalation process is governed by the non-covalent stacking (including charge-transfer) interaction while the hydrogen bonding between the ethidium amino groups and the DNA backbone is less important. This is confirmed by the evaluation of the interaction energy as well as by the calculation of the free energy change. The intercalation affects the macroscopic properties of DNA in terms of its flexibility. This explains the easier entry of another intercalator molecule in the vicinity of an existing intercalation site.
采用相关的从头算以及半经验量子化学计算和分子动力学模拟来研究阳离子乙锭、阳离子5-乙基-6-苯基菲啶鎓和不带电荷的3,8-二氨基-6-苯基菲啶对DNA的嵌入。阳离子嵌入剂的稳定能比不带电荷的嵌入剂大得多。所有嵌入剂的主要能量贡献由色散能表示。对于阳离子嵌入剂，静电和电荷转移项也很重要。乙锭嵌入DNA的ΔG估计为-4.5 kcal mol⁻¹，该值与实验结果吻合良好。对最终自由能的六种贡献中，相互作用能值至关重要。嵌入过程由非共价堆积（包括电荷转移）相互作用控制，而乙锭氨基与DNA主链之间的氢键作用不太重要。这通过相互作用能的评估以及自由能变化的计算得到证实。嵌入在DNA的柔韧性方面影响其宏观性质。这解释了另一个嵌入剂分子在现有嵌入位点附近更容易进入的现象。
