| 包珊珊,胡光,胡华四.质子辐射诱导B-DNA沟槽损伤产额的模拟研究[J].中华放射医学与防护杂志,2026,46(8):740-748.Bao Shanshan,Hu Guang,Hu Huasi.A simulation study on the yields of proton irradiation-induced groove damage in B-DNA[J].Chin J Radiol Med Prot,2026,46(8):740-748 |
| 质子辐射诱导B-DNA沟槽损伤产额的模拟研究 |
| A simulation study on the yields of proton irradiation-induced groove damage in B-DNA |
| 投稿时间：2026-03-17 |
| DOI：10.3760/cma.j.cn112271-20260317-00103 |
| 中文关键词: 质子|DNA大沟|DNA小沟|Geant4-DNA|PDB4DNA |
| 英文关键词:Proton|DNA major groove|DNA minor groove|Geant4-DNA|PDB4DNA |
| 基金项目:国家自然科学基金(11975182) |
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| 中文摘要: |
| 目的 从纳米尺度模拟研究质子辐射诱导B-DNA大沟/小沟损伤(MBD/mBD)与结构参数二核苷酸步阶(step)、沟槽宽度(大沟宽MW、小沟宽mW)及糖-磷酸基团(S-P基团)的关联性。方法 基于生物信息学工具,剖析四核小体晶体结构(PDBID: 1ZBB)的空间构象组成,选取该结构中局部B-DNA作为研究靶序列。之后,基于Geant4-DNA完成质子辐射诱导B-DNA损伤,并获取其中的沟槽损伤数据。基于Watson-Crick碱基对大/小沟的原子组成,分别量化大/小沟槽损伤产额(YMBD/YmBD),实现沟槽损伤在原子尺度上的精确表征。结果 传能线密度(LET)为55.04 keV/μm的质子照射B-DNA后,B-DNA中YMBD和YmBD随step数目的增多而增大,其中YMBD平均值(3.27 Gy-1·Gbp-1)大于YmBD平均值(1.65 Gy-1·Gbp-1);通过LET为2.59~62.93 keV/μm的质子照射B-DNA,研究B-DNA的沟槽损伤产额与S-P基团之间的关联性发现,随着LET的增大,B-DNA中YMBD随之增大,增长率为10.40%;大沟的损伤概率(PMBD)随之减小,减少率为9.66%;YmBD及小沟的损伤概率(PmBD)均随LET的增大而增大,二者的增长率分别为48.76%和23.64%。此外,B-DNA的小沟槽能量沉积(EmBD)和YmBD均小于大沟槽能量沉积(EMBD)和YMBD。结论 B-DNA中沟槽损伤产额与step数目呈正相关,但与沟槽宽度无显著相关性;S-P基团对小沟具有显著的辐射保护作用,能有效降低其辐射损伤程度,但该保护作用随质子LET的增大而逐渐降低。 |
| 英文摘要: |
| Objective To conduct a nanoscale simulation study on the correlations of proton irradiation-induced damage to the major and minor grooves in B-DNA (also referred to as MBD and mBD, respectively) with DNA structural parameters, including the dinucleotide step, major and minor groove widths (denoted by MW and mW, respectively), and sugar-phosphate groups (also referred to as the S-P groups). Methods The spatial conformation of the crystal structure of a tetranucleosome (PDB ID: 1ZBB) was analyzed using bioinformatics tools, with partial B-DNA segments in the structure selected as target sequences. Proton irradiation-induced B-DNA damage was then simulated using the Geant4-DNA toolkit, and data on groove damage were acquired. Baseed on the atomic composition of major and minor grooves in Watson-Crick base pairs, the yields of MBD and mBD (denoted by YMBD and YmBD, respectively) were quantified, thus achieving the precise atomic-scale characterization of groove damage. Results After B-DNA was exposed to proton irradiation with a linear energy transfer (LET) of 55.04 keV/μm, both YMBDand YmBD in B-DNA increased as the number of dinucleotide steps increased, with the average YMBD (3.27 Gy-1·Gbp-1) higher than the average YmBD (1.65 Gy-1·Gbp-1). The correlations between groove damage and the S-P groups were investigated by exposing B-DNA to proton irradiation with LET ranging from 2.59 to 62.93 keV/μm. The result indicated that with increasing LET, the YMBD in B-DNA increased at a rate of 10.40%, the probability of MBD (PMBD) declined at a rate of 9.66%, and YmBD and the probability of mBD (PmBD) increased at rates of 48.76% and 23.64%, respectively. In addition, the energy deposition of the minor groove (EmBD) and YmBD were lower than the energy deposition of the major groove (EMBD) and YMBD, respectively. Conclusions There are positive correlations between the yields of groove damage in B-DNA and the number of dinucleotide steps, while there is a lack of significant correlations between them and the groove widths. The S-P groups play a significant role in protecting the minor groove against proton irradiation; however, such protection weakens with increasing the LET of proton irradiation. |
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