Aydogan Bulent, Bolch Wesley E, Swarts Steven G, Turner James E, Marshall David T
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637, USA.
Radiat Res. 2008 Feb;169(2):223-31. doi: 10.1667/RR0293.1.
An atomistic biophysical model permitting the calculation of initial attacks to a 38-bp representation of B-DNA base moieties by water radicals is presented. This model is based on a previous radiation damage model developed by Aydogan et al. (Radiat. Res. 157, 38-44, 2002). Absolute efficiencies for radical attack to the 38-bp DNA molecule are calculated to be 41, 0.8 and 15% for hydroxyl radical ((.)OH), hydrogen radical (H(.)), and hydrated electron (e(aq))(,) respectively. Among the nucleobases, guanine is found to have the highest percentage (.)OH attack probability at 36%. Adenine, cytosine and thymine moieties have initial attack probabilities of 24, 18 and 22%, respectively. A systematic study is performed to investigate (.)OH attack probabilities at each specified attack site in four molecular models including free bases, single nucleotides, single base pairs, and the central eight base pairs of the 38-bp DNA molecule. Cytosine is the free base moiety for which the closest agreement is observed between the model prediction and the experimental data. The initial (.)OH attack probabilities for cytosine as the free base are calculated to be 72 and 28%, while experimental data are reported at 87 and 13% for the C5 and C6 positions on the base, respectively. In this study, we incorporated atomic charges to scale the site-specific (.)OH reaction rates at the individual atomic positions on the pyrimidine and purine bases. Future updates to the RIDNA model will include the use of electron densities to scale the reaction rates. With respect to reactions of the aqueous electron with DNA, a comparison of the initial distribution of electron attack sites calculated in this study and experimental results suggests an extremely rapid and extensive redistribution of the e(-)(aq) after their initial reactions with DNA.
提出了一种原子生物物理模型，该模型能够计算水自由基对38个碱基对的B - DNA碱基部分的初始攻击。此模型基于艾多安等人（《辐射研究》157卷，38 - 44页，2002年）之前开发的辐射损伤模型。计算得出，羟基自由基（·OH）、氢自由基（H·）和水合电子（e(aq)）对38个碱基对的DNA分子的自由基攻击绝对效率分别为41%、0.8%和15%。在这些碱基中，鸟嘌呤被发现受到·OH攻击的概率最高，为36%。腺嘌呤、胞嘧啶和胸腺嘧啶部分的初始攻击概率分别为24%、18%和22%。进行了一项系统研究，以调查在包括游离碱基、单核苷酸、单碱基对以及38个碱基对的DNA分子的中央八个碱基对在内的四个分子模型中，每个特定攻击位点的·OH攻击概率。胞嘧啶是在模型预测与实验数据之间观察到最接近一致性的游离碱基部分。作为游离碱基的胞嘧啶的初始·OH攻击概率计算为72%和28%，而实验数据分别报道该碱基上C5和C6位置的攻击概率为87%和13%。在本研究中，我们纳入了原子电荷以缩放嘧啶和嘌呤碱基上各个原子位置的位点特异性·OH反应速率。RIDNA模型的未来更新将包括使用电子密度来缩放反应速率。关于水合电子与DNA的反应，本研究中计算的电子攻击位点的初始分布与实验结果的比较表明，e(-)(aq)在与DNA发生初始反应后会极其迅速且广泛地重新分布。
