Anharmonic Vibrational Signatures of DNA Bases and Watson-Crick Base Pairs

Changes of molecular structure and associated charge distributions, and changes of anharmonic vibrational parameters from DNA base monomers to the Watson-Crick base pairs, have been investigated at the density functional theory level. Through examination of the NH2, N H, and C=O stretching vibrational modes that are involved in the multiple H-bonds in the base pairs, sensitivity of their diagonal and off-diagonal anharmonicities, as well as anharmonic vibrational couplings, to the structure change are predicted. Our results reveal the intrinsic connection between the anharmonic vibrational potentials, H-bonding, and electrostatic interactions in DNA bases.

Detection of DNA Bases Using Fe Atoms and Graphene

The adsorption of DNA bases on a magnetic probe composed of Fe atoms and graphene is studied by using first- principles calculations. The stability of geometry, the electronic structure and magnetic property are investigated. The results indicate that four DNA bases, i.e., adenine, thymine, cytosine and guanine, can all be adsorbed on the probe solidly. However, the magnetic moments of the composite structure can be observed only when adenine adsorbs on the probe. In the cases of the adsorption of the other three bases, the magnetic moments of the composite structure are zero. Based on the significant change of magnetic moment of the composite structure, adenine can be distinguished conveniently from thymine, cytosine and guanine. This work may provide a new way to detect DNA bases.

Covalent coupling of DNA bases with graphene nanoribbon electrodes: Negative differential resistance, rectifying, and thermoelectric performance

By applying nonequilibrium Green's functions in combination with the density-functional theory, we investigate the electronic, thermal, and thermoelectric properties of four kinds of bases in DNA perpendicularly coupling between two ZGNR electrodes. The results show that the electron transport is highly sensitive to different base-ZGNR coupling geometries, and the system can present large rectifying and negative differential resistance effects. Moreover, the fluctuations of electronic transmission and super-low thermal conductance result in significant enhancement of the thermoelectric figure of merit (ZT): the ZT will be over 1.4 at room temperature, and over 1.6 at 200 K. The results show that the base-ZGNR coupling devices can present large rectifying, negative differential resistance, and enhanced thermoelectric effects.

DFT Study on Reaction Mechanism of DNA Base Pair with Hydroxyl Radical

In order to elucidate the indirect effect by radiation on DNA base pairs, we investigate the mechanism for the attacking reaction of a hydroxyl radical (·OH-radical) to the G-C and A-T base pairs, by the density functional theory (DFT) calculations. The effect of solvation on the mechanism is also revealed by performing the same DFT calculations under the continuum solvation approximation. We find the stable structures for the dehydrogenated G-C and A-T base pairs, in which the hydrogen atom of NH2 group of G or A base is abstracted by the ·OH-radical. The solvation around the base pairs stabilizes the dehydrogenated structures significantly, indicating the acceleration of the attacking reaction by ·OH-radical to the base pairs in water. Therefore, we conclude that the hydrogen atom of the NH2 group of G or A base in the G-C and A-T base pairs is the most preferably abstracted by the ·OH-radical in living cells.

DNA-based方法及其在研究动物食物组成中的应用

了解动物的食物组成是研究生态系统的多样性和生态系统功能的基本要求,在动物生态学的研究中至关重要。DNA-based方法包括样本采集、DNA提取、PCR扩增、序列比对分析等一系列步骤,实验的成败取决于标记基因的选择、引物的设计及每个步骤的优化。文章综述了DNA-based方法的各个基本步骤及其优化方法,并对该方法在今后用于国内相关研究的可能性进行展望,关注用于研究国内三峡大坝这个大型水域生态系统的可能性,期望推动国内该领域的研究。

5-硝基水杨醛氨基酸Schiff-bases铜配合物与DNA相互作用的研究

用电子光谱、荧光淬灭光谱和循环伏安的方法,研究了(苯丙氨酸缩5-硝基水杨醛)铜(1)和(组氨酸缩5-硝基水杨醛)铜(2)与 DNA 的作用.结果表明,配合物均以插入模式与 DNA 作用;配合物与 DNA 作用强弱为:配合物(2)>配合物(1).

Effect of interaction between loop bases and ions on stability of G-quadruplex DNA

G-quadruplexes(GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. The topology of GQs is associated with the sequences and lengths of DNA, the types of linking loops, and the associated metal cations. However, our understanding on the basic physical properties of the formation process and the stability of GQs is rather limited. In this work, we employed ab initio, molecular dynamics(MD), and steered MD(SMD)simulations to study the interaction between loop bases and ions, and the effect on the stability of G-quadruplex DNA, the Drude oscillator model was used in MD and SMD simulations as a computationally efficient manner method for modeling electronic polarization in DNA ion solutions. We observed that the binding energy between DNA bases and ions(K^(+)/Na^(+))is about the base stacking free energies indicates that there will be a competition among the binding of M^(+)-base, H-bonds between bases, and the base-stacking while ions were bound in loop of GQs. Our SMD simulations indicated that the side loop inclined to form the base stacking while the loop sequence was Thy or Ade, and the cross-link loop upon the G-tetrads was not easy to form the base stacking. The base stacking side loop complex K+was found to have a good stabilization synergy. Although a stronger interaction was observed to exist between Cyt and K+, such an interaction was unable to promote the stability of the loop with the sequence Cyt.

Mechanistic Study on the Monofunctional Binding of Hydrolysis Products of Non-planar Heterocyclic Complexes Trans-[PtCl_2NH_3(piperidine)] and Trans-[PtCl_2(piperidine)_2] to DNA Purine Bases

The monofunctional substitution reactions between trans-[PtCl（H2O）（NH3）（pip）]＋,trans-[Pt（H2O）2（NH3）（pip）]2＋,trans-[PtCl（H2O）（pip）2]＋,trans-[Pt（H2O）2（pip）2]2＋ （pip = piperidine） and adenine/guanine nucleotides are explored by using B3LYP hybrid functional and IEF-PCM salvation models. For the trans-[Pt（H2O）2（NH3）（pip）]2＋ and trans-[PtCl（H2O）（NH3）（pip）]＋ complexes,the computed barrier heights in aqueous solution are 13.5/13.5 and 11.6/11.6 kcal/mol from trans-Pt-chloroaqua complex to trans/cis-monoadduct for adenine and guanine,and the corresponding values are 20.7/20.7 and 18.8/18.8 kcal/mol from trans-Pt-diaqua complex to trans/cis-monoadduct for adenine and guanine,respectively. For trans-[PtCl（H2O）（pip）2]＋ and trans-[Pt（H2O）2（pip）2]2＋,the corresponding values are 21.5/21.3 and 19.4/19.4 kcal/mol,and 26.0/26.0 and 20.7/20.8 kal/mol for adenine and guanine,respectively. Our calculations demonstrate that the barrier heights of chloroaqua are lower than the corresponding values of diaqua for adenine and guanine. In addition,the free energies of activation for guanine in aqueous solution are all smaller than that for adenine,which predicts a preference of 1.9 kcal/mol when trans-[PtCl（H2O）（NH3）（pip）]＋ and trans-[Pt（H2O）2（NH3）（pip）]2＋ are the active agents and ～1.9 and ～ 5.3 kcal/mol when trans-[PtCl（H2O）（pip）2]＋ and trans-[Pt（H2O）2（pip）2]2＋ are the active agents,respectively. For the reaction of trans-Pt-chloroaqua （or diaqua） to cis-monoadduct,we obtain the same transition-state structure as from the reaction of trans-Pt-chloroaqua （or diaqua） to trans-monoadduct,which seems that the trans-Pt-chloroaqua （or diaqua） complex can generate trans-or cis-monoadduct via the same transition-state.

Molecular modeling study of the effect of base methylation on internal interactions and motions in DNA and implication to B-Z conformation change

Methylation in the bases of DNA is known to induce B-Z conformation change. In this work, molecular mechanics and normal mode analysis are used to probe how certain methylation affects the internal interactions and thermodynamic motions in the DNA double helixes in both B and Z conformations, and its implication to B-Z conformation change. By molecular modeling with Insight II, two cases involving cytosine C5 and guanine C8 methylation on both B and Z-form DNA duplex d(CGCGCG)2 are studied in comparison with the corresponding unmethylated duplexes. The internal interaction energies computed based on a molecular mechanics force field and the entropies due to internal motions computed according to a normal mode analysis are in fare agreement with respective observed thermodynamic quantities. The analysis on the computed individual energy terms suggests that the observed B-Z conformation change induced by methylation is primarily driven by enthalpic factors. A combination of changes in Van der Waals interaction, electrostatic interaction and hydrogen bonding likely contributes to the change of enthalpy that favors Z-conformation in the methylated states.

Integrated DNA-based/biochemical screening for early diagnosis of multiple endocrine neoplasia type 2A (MEN2A)

Multiple endocrine neoplasia type 2A （MEN2A）, a subtype of MEN2, is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A Han Chinese pedigree with MEN2A was investigated following confirmation of the proband＇s diagnosis by pathological findings and DNA/biochemical screening. DNA samples from 4 other family members were collected and exon 5, 8, 10, 11, 13, 16 and 18 of the RET proto-oncogene were sequenced and then analyzed. A missense mutation of TGG （Trp） to TGC （Cys） at codon 634 （the classic MEN2A mutation） in exon 11 of the RET gene was detected in 3 family members, including the proband. Sequencing data were compared with the human gene mutation database. Elevated serum calcitonin level was detected initially; medullary thyroid carcinoma was revealed in the 3 cases and adrenal pheochromocytoma was also found in the proband. Elective operations were successfully performed on the adrenal and thyroid glands because of pheochromocytoma and medullary thyroid carcinoma. Our case study confirms that integrated DNA-based/biochemical screening is crucial for early diagnosis of MEN2A and is helpful in the screening of their relatives. In addition, DNA-based screening may occasionally uncover a previously unknown RET sequence.

An ionic liquid supported CeO_2 nanoparticles-carbon nanotubes composite-enhanced electrochemical DNA-based sensor for the detection of Pb^(2+)

An electrochemical sensor incorporating a signal enhancement for the determination of lead （II） ions （Pb2＋） was designed on the basis of the thrombin-binding aptamer （TBA） as a molecular recog- nition element and ionic liquid supported cerium oxide （CeO2） nanoparticles-carbon nanotubes compo- site modification. The composite comprises nanoparticles CeO2, multi-waU carbon nanotubes （MWNTs） and hydrophobic room temperature ionic liquid （RTIL） 1-ethyl-3-methylimidazolium tetrafluoroborate （EMIMBF4）. The electrochemical sensors were fabricated by immersing the CeOa-MWNTs-EMIMBF4 modified glassy carbon electrode （GCE） into the solution of TBA probe. In the presence of Pb2＋, the TBA probe could form stable G-quartet structure by the specific binding interactions between Pb2＋ and TBA. The TBA-bound Pb2＋ can be electrochemically reduced, which provides a readout signal for quantitative detection of Pb2＋. The reduction peak current is linearly related to the concentration of Pb2＋ from 1.0 ＊ 10-8 M to 1.0 ＊ 105 M with a detection limit of 5 ＊ 109 M. This work demonstrates that the CeOz-MWNTs-EMIMBF4 nanocomposite modified GCE provides a promising platform for immobi- lizing the TBA probe and enhancing the sensitivity of the DNA-based sensors.

DNA存储系统中的数据写入

世界的数字化给人们的生活带来了极大的变化,但与此同时,史无前例的数据激增使得信息存储面临的挑战日益严峻。随着全球数据总量的指数级增长,传统存储介质将无法满足数字化带来的存储需求。使用DNA分子作为基本载体的信息存储展现出高存储密度、低维护成本和易于化学修饰等独特优势。DNA存储主要包括编码、写入、保存、检索、读取和解码六个主要步骤,其中数据的写入是实现DNA存储功能的基础。本文首先介绍DNA存储系统中体外写入数据的策略方法,主要分为将数据写入DNA序列和写入DNA结构两个部分,接着概述体内写入数据技术的发展,最后将讨论DNA存储系统中数据写入面临的写入成本高、写入速度慢等挑战,并对大规模合成高纯度DNA、改进生物酶等具有前景的应用技术进行展望。

激发态DNA碱基对分子间相互作用的理论研究

[目的]利用本课题组发展的定量分析方法研究激发态DNA碱基对分子间相互作用的本质,以及不同类型的电子跃迁对DNA碱基对分子间相互作用的影响.[方法]采用广义Kohn-Sham能量分解分析方法(generalized Kohn-Sham based energy decomposition analysis,GKS-EDA),对两种Waston-Crick构型和两种stacked构型的DNA碱基对分子间相互作用本质进行理论研究.[结果]对于Waston-Crick构型的碱基对,n→π^(*)跃迁削弱了轨道极化作用但加强了电子相关作用,激发态分子间相互作用由电子相关作用主导,而π→π^(*)跃迁对分子间氢键影响较小;对于stacked构型的碱基对,π→π^(*)跃迁削弱了静电相互作用但增强了电子相关作用.[结论]Waston-Crick构型碱基对分子间相互作用本质受电子激发跃迁影响较大,而电子激发跃迁基本不改变stacked构型碱基对分子间相互作用本质.

Novel Transient Species of DNA Bases From Laser Photolysis

The laser photochemistry and photosensitization of DNA bases were carried out by using a nanosecond kinetic spectroscopy. A novel triplet state of thymine and its OH adduct were observed in N_2 and N_2O saturated aqueous solution respectively. The transient absorption spectra of triplet cytosine, cytidine and deoxycytidine monophosphoric acid were observed for the first time. Triplet guanosine was confirmed and its pK, value, 8.7, was obtained. Kinetic studies of the growth-decay of the above transient species were performed and their reaction mechanisms were elucidated in detail.

DNA Interaction and Cytotoxic Activity of a Chiral Amino-alcohol Schiff Base Derived Cu(Ⅱ) Complex

A novel copper（Ⅱ） complex based on chiral amino-alcohol derived Schiff base ligand,[Cu_4（R-L）_4（H_2O）_2]·（CH_3COOH）_2·（H_2O）（1,（R）-H_2 L =（R）-3-phenyl-2-（2-hydroxy-3-methoxybenzylideneamino） propane-1-ol）,was synthesized and characterized by EA,IR,UV-Vis,ESI-MS,circular dichroism spectra and single-crystal X-ray diffraction.Complex 1 crystallizes in orthorhombic,space group Ρ2_12_12 with a = 15.7660（14）,b = 49.526（3）,c = 10.4213（9） A,V = 8137.2（12） A^3,Ζ = 4,C_（72）H_（81）Cu_4N_4O_（19）,Mr = 1560.57,μ = 1.096 mm^-1,F（000） = 3244,Flack = 0.06（3）,the final R = 0.0924 and w R = 0.2451（I 〉 2σ（I）） for 41108 observed reflections.The interactions of the complex with calf thymus DNA（CT-DNA） were investigated by some spectroscopic technique methods.The results show the complex exhibits strong binding with CT-DNA.In addition,in vitro cytotoxicity test of 1 towards four kinds of human cancerous cell lines（He La,HL-60,Caco-2 and A549） showed substantial cytotoxic activity.The experimental investigations indicated that the chirality of complex 1 play an important role in cytotoxicity and interactions with DNA.

DNA倍体分析对液基细胞学在良恶性胸腹水诊断中的支持价值

目的:探讨液基细胞学、肿瘤标志物和DNA倍体分析单独和联合在良恶性胸腹水诊断中的鉴别价值。方法:收集312例同时做过胸腹水液基细胞学检查、DNA倍体分析和血清肿瘤标志物检测的病例,且所有病例都有组织病理诊断结果,对这些指标及人口统计学特征进行分析;基于液基细胞学、肿瘤标志物、DNA倍体分析单独及其组合的诊断,通过Logistic回归建立组合模型,并通过ROC曲线下面积(AUC)进行比较,以及计算其对应的敏感度(SE)、特异度(SP)、阳性预测值(PPV)和阴性预测值(NPV)。结果:以组织病理诊断结果为金标准,液基细胞学、肿瘤标志物和DNA倍体分析的AUC值分别是0.702、0.512、0.776;模型1(液基细胞学联合肿瘤标志物)AUC值为0.722,SE为49.8%,SP为90.6%,PPV为79.5%,NPV为24.5%;模型2(液基细胞学联合DNA倍体分析)AUC值为0.783,SE为68.7%,SP为83.00%,PPV为95.2%,NPV为35.2%;模型3(模型2联合肿瘤标志物)AUC值0.776,SE为58.7%,SP为88.7%,PPV为85.3%,NPV为29.8%;模型2表现出对良恶性胸腹水最高的诊断效率,液基细胞学和DNA倍体分析组合的AUC值高于液基细胞学(P<0.0001)和DNA倍体分析(P=0.3998)。结论:DNA倍体分析的诊断价值高于液基细胞学和传统肿瘤标志物;DNA倍体分析对液基细胞学在良恶性胸腹水的诊断中具有支持价值,提供了一种鉴别良恶性胸腹水的可靠模式。

Solving the independent set problem by sticker based DNA computers

In this paper, the sticker based DNA computing was used for solving the independent set problem. At first, solution space was constructed by using appropriate DNA memory complexes. We defined a new operation called “divide” and applied it in construction of solution space. Then, by application of a sticker based parallel algorithm using biological operations, independent set problem was resolved in polynomial time.

Applying Surface-Based DNA Computing for Solving the Dominating Set Problem

The surface-based DNA computing is one of the methods of DNA computing which uses DNA strands immobilized on a solid surface. In this paper, we applied surface-based DNA computing for solving the dominating set problem. At first step, surface-based DNA solution space was constructed by using appropriate DNA strands. Then, by application of a DNA parallel algorithm, dominating set problem was resolved in polynomial time.

Applying DNA Computation to Error Detection Problem in Rule-Based Systems

As rule-based systems (RBS) technology gains wider acceptance, the need to create and maintain large knowledge bases will assume greater importance. Demonstrating a rule base to be free from error remains one of the obstacles to the adoption of this technology. In the past several years, a vast body of research has been carried out in developing various graphical techniques such as utilizing Petri Nets to analyze structural errors in rule-based systems, which utilize propositional logic. Four typical errors in rule-based systems are redundancy, circularity, incompleteness, and inconsistency. Recently, a DNA-based computing approach to detect these errors has been proposed. That paper presents algorithms which are able to detect structural errors just for special cases. For a rule base, which contains multiple starting nodes and goal nodes, structural errors are not removed correctly by utilizing the algorithms proposed in that paper and algorithms lack generality. In this study algorithms mainly based on Adleman’s operations, which are able to detect structural errors, in any form that they may arise in rule base, are presented. The potential of applying our algorithm is auspicious giving the operational time complexity of O(n*(Max{q, K, z})), in which n is the number of fact clauses;q is the number of rules in the longest inference chain;K is the number of tubes containing antecedents which are comprised of distinct number of starting nodes;and z denotes the maximum number of distinct antecedents comprised of the same number of starting nodes.

纸基法血液基因组DNA的提取与应用

建立一种提取小鼠血液中基因组DNA的纸基方法进行分子鉴定和基因分型,选择试剂盒提取法和常规煮沸法作为对比,分别对10只基因敲除型小鼠后代组织的基因组DNA进行提取,用多基因PCR扩增进行鉴定,随机选择2只小鼠的鉴定结果进行测序验证。PCR均扩增出符合预期大小的条带,验证了纸基法的稳定性和特异性。3种DNA提取方法的PCR扩增结果表明,试剂盒提取法与纸基法提取效果相似,共鉴定出4只野生型小鼠,5只基因敲除杂合型小鼠和1只基因敲除型纯合型小鼠;煮沸法对小鼠基因型DNA提取效果较差。测序分析结果显示,基因类型与纸基法鉴定基因类型一致。用纸基法提取基因组DNA不需要专业设备就可满足小鼠血液基因组DNA的提取及下游试验,可为基因型鉴定提供一种可靠快速的方法。