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国家自然科学基金(11274374)

作品数:5 被引量:1H指数:1
相关作者:吕袭明尤菁李伟奚绪光窦硕星更多>>
相关机构:中国科学院大学中国科学院西北农林科技大学更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划更多>>
相关领域:生物学理学更多>>

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单分子荧光共振能量转移数据处理的优化算法
2017年
单分子荧光共振能量转移(smFRET)技术是当今单分子生物物理研究领域的重要实验手段,该技术通过测量供体、受体荧光光强以及二者间的共振能量转移效率,揭示标记位点间的距离,用于研究DNA、蛋白质等生物大分子的构象变化.然而,当前传统数据处理方法大量依赖人工干预,噪音大,严重影响了实验效率和数据的可靠性.本文提出了一种针对smFRET数据的自动分析算法.该算法主要包括三个部分:基于计算供体与受体荧光光强的相关系数来确定受体与供体对应荧光点的自动匹配算法、甄别错误点的筛选算法以及基于隐马尔可夫模型的全局拟合算法.经改进后的算法大大简化了传统算法中需要人工干预的步骤,而且自动筛除了实验数据中主要的几类噪音.将改进的算法应用于人类端粒重复序列G-四联体(G4)DNA折叠动力学的数据分析,结果显示优化算法比传统算法能够更快地得到更高信噪比的数据,而且该数据结果清晰地表明G4的折叠体现出多态性并受到钾离子浓度的影响.
吕袭明李辉尤菁李伟王鹏业李明奚绪光窦硕星
关键词:折叠动力学
Effects of oxaliplatin on DNA condensation
2014年
In this paper the interactions between DNA and anti-cancer drug oxaliplatin were investigated by using magnetic tweezers.The dynamics of DNA condensation due to oxaliplatin was traced under various forces.It is found that torsion constraint in DNA enhances the ability of oxaliplatin for shortening DNA.The transplatin helps oxaliplatin combine to DNA and increase the rate of DNA condensation.All these results are consistent to the previously proposed model and are helpful for further investigation of interaction between DNA and oxaliplatin.
JU HaiPengZHANG HongYanLI WeiWANG PengYe
关键词:奥沙利铂DNA抗癌药缩合
Brownian ratchet mechanism of translocation in T7 RNA polymerase facilitated by a post-translocation energy bias arising from the conformational change of the enzyme
2017年
T7 RNA polymerase can transcribe DNA to RNA by translocating along the DNA. Structural studies suggest that the pivoting rotation of the O helix in the fingers domain may drive the movement of the O helix C-terminal Tyr639 from pre- to post-translocation positions. In a series of all-atom molecular dynamics simulations, we show that the movement of Tyr639 is not tightly coupled to the rotation of the O helix, and that the two processes are only weakly dependent on each other. We also show that the internal potential of the enzyme itself generates a small difference in free energy (△E) between the post- and pre-translocation positions of Tyr639. The calculated value of △E is consistent with that obtained from single-molecule experimental data. These findings lend support to a model in which the translocation takes place via a Brownian ratchet mechanism, with the small free energy bias △E arising from the conformational change of the enzyme itself.
王展峰张志强付一本王鹏业谢平
Local conformation transitions of linear DNA induced by cisplatin被引量:1
2014年
Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.
Chao JiLingyun ZhangShuoxing DouPengye Wang
关键词:DNA分子构象转变原子力显微镜构象转换
Helicase activity and substrate specificity of RecQ5β
2017年
RecQ5β is an essential DNA helicase in humans, playing important roles in DNA replication, repair, recombination and transcription. The unwinding activity and substrate specificity of RecQ5β is still elusive. Here, we used stopped-flow kinetic method to measure the unwinding and dissociation kinetics of RecQ5β with several kinds of DNA substrates, and found that RecQ5β could well unwind ss/ds DNA, forked DNA and Holiday junction, but was compromised in unwinding blunt DNA and G-quadruplex. Rec5β has the preferred unwinding specificity for certain DNA substrates containing the junction point, which may improve the binding affinity and unwinding activity of RecQ5β. Moreover, from a comparison with the truncated RecQ5β~(1-467), we discovered that the C-terminal domain might strongly influence the unwinding activity and binding affinity of RecQ5β. These results may shed light on the physiological functions and working mechanisms of RecQ5β helicase.
尤菁徐雅楠李辉吕袭明李伟王鹏业窦硕星奚绪光
关键词:HELICASEDNA
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