MOLECULAR DYNAMICS SIMULATIONS OF METAL-CONTAINING MODIFIED PNA DUPLEXES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肽核酸(PNA)是一种合成的DNA类似物，含有相同的 碱基，如DNA中的碱基，但其中的糖磷酸被一种 结构同态的伪肽链。沃森·克里克的PNA表格 碱基对与DNA同构的双链。PNA链可以结合 到其他PNA链%2C到DNA和RNA。此文件中请求的计算机时间 应用程序将用于研究含金属的替代碱基对 这可以在PNA中引入。对这些替代基准点的追求已经 生物相关性，因为它将提供相关信息来评估 这些基对利用配位键存储信息的潜力 而不是以类似于遗传密码的方式的氢键%2C。 此外，新的PNA-金属杂化分子具有可以 用于分子电子学应用。分子中的主要冲刺 电子学是对纳米尺度的新分子的发现 可用作分子导线或装置以及它们的组装方法 纳米级电路中的分子。 我们发现，肽核酸(PNA)%2C是一种合成的类似物 DNA%2C可作为碱基取代的金属离子支架 在具有对金属离子具有高亲和力的配体的PNA低聚物中 PNA双面打印。因此，修改后的双工通过 氢键和配位键的结合。我们将此策略用于 含Tm离子纳米结构的可控组装 配体修饰的PNA螺旋双链。 我们的方法可以控制金属离子的类型和位置 结合在双链中，使我们能够将Tm离子放置在特定的 在一维结构中的位置，并产生相当长的金属阵列。 这项提议的具体目标是使用分子动力学模拟来 探索含金属的PNA双链的结构。最新分子 PNA-PNA和PNA-DNA双链的动力学研究表明，PNA链保持 稳定的双螺旋结构。模拟开始于A-DNA或 B-DNA融合为PNA结构，与已报道的核磁共振结果一致 和结晶学观察。 核酸支架的初始坐标将从B-DNA中获得 典型的双螺旋结构，序列与P相同。 主链将被替换为肽主链%2C PNA和DNA原子之间的对应关系。 我们计划使用的分子动力学软件是琥珀。力场 第94段将与以前确定的PNA参数相补充 我的脊梁。%5BPT(联吡啶)2%5D2%2B的配位和电荷已经 由我们实验室的学生使用Gaussian98和B3LYP混合获得 泛函和标准LANL2DZ基组。PNA原子的电荷也是 已使用HF%2F6-31G%2A基组获得。 我们请求在Ben上提供30%2C000个服务单位以启动 模拟并获得基准。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Peptide nucleic acids (PNA) are synthetic analogs of DNA which contain the same nucleobases as those in DNA but in which the sugar phosphate is replaced by a structurally homomorphous pseudopeptide chain. PNA forms by Watson Crick basepairing duplexes that are homomorphous to DNA ones. PNA strands can bind to other PNA strands%2C to DNA and to RNA. The computer time requested in this application will be used to investigate metal-containing alternative base pairs that can be introduced in PNA. The pursuit of these alternative basepairs has biological relevance because it will provide information relevant to assess the potential of these basepairs to store information by using coordinative bonds instead of hydrogen bonds%2C in a manner similar to that of the genetic code. In addition, the new hybrid PNA-metal molecules have properties that can be used in molecular electronics applications. Major thrusts in molecular electronics are the discovery of new molecules with nanometer dimensions that can function as molecular wires or devices and of methods for assembly of these molecules in nanosize circuits. We have discovered that peptide nucleic acid (PNA)%2C a synthetic analog of DNA%2C can be used as scaffold for metal ions by substitution of nucleobases within PNA oligomers with ligands that confer high affinity for metal ions to the PNA duplexes. As a consequence, the modified duplexes are bridged by a combination of hydrogen and coordinative bonds. We use this strategy for the controlled assembly of nanostructures containing TM ions based on ligand-modified PNA helical duplexes. Our approach offers control over the type and position of metal ions incorporated in the duplexes and enables us to place TM ions at specific locations in 1-D structures and to create metal arrays of sizable length. The specific goal of this proposal is to use molecular dynamics simulations to explore the structure of metal-containing PNA duplexes. Recent molecular dynamics studies of PNA-PNA and PNA-DNA duplexes show that PNA strands maintain stable double helical structures. Simulations started with either A-DNA or B-DNA converged to PNA structures that were in good agreement with reported NMR and crystallographic observations. Initial coordinates for the nucleic acid scaffold will be obtained from a B-DNA canonical double-helix with the same sequence as P. The sugar-phosphate backbone will be replaced with the peptide backbone%2C according to the correspondence between the PNA and DNA atoms. The molecular dynamics software that we plan to use is AMBER. The force field parm94 will be complemented with previously determined parameters for the PNA backbone. Coordinates and charges for %5BPt(bypiridine)2%5D2%2B have already been obtained by students in our lab using Gaussian98 with the B3LYP hybrid functional and the standard LANL2DZ basis set. Charges for PNA atoms were also already obtained using an HF%2F6-31G%2A basis set. We are requesting a starting grant of 30%2C000 service units on ben to initiate the simulations and obtain benchmarks.