MOLECULAR DYNAMICS SIMULATIONS OF METAL-CONTAINING MODIFIED PNA DUPLEXES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肽核酸（PNA）是DNA的合成类似物，其含有相同的 核碱基与DNA中的核碱基一样，但其中磷酸糖被取代， 结构同形假肽链。 沃森克里克的PNA形式 与DNA同形的碱基配对双链体。 PNA链可以结合 与其它PNA链，与DNA和RNA连接。 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 可以在PNA中引入。对这些替代碱基对的追求 生物相关性，因为它将提供相关信息，以评估 这些碱基对通过配位键储存信息的潜力 而不是以类似于遗传密码的方式形成氢键。 此外，新的混合PNA-金属分子具有可以 用于分子电子学应用。 分子生物学领域的主要进展 电子学是发现具有纳米尺寸的新分子， 可以用作分子线或器件，以及组装这些的方法 纳米电路中的分子。 我们已经发现肽核酸（PNA）2C是肽核酸的合成类似物， DNA%2C可通过取代核碱基作为金属离子的支架 在PNA寡聚体中，配体赋予金属离子高亲和力， PNA双链体。 因此，经修饰的双链体通过一个 氢和配位键的组合。 我们将此策略用于 含有TM离子的纳米结构的受控组装， 配体修饰的PNA螺旋双链体。 我们的方法可以控制金属离子的类型和位置 结合在双链体中，使我们能够将TM离子置于特定的位置， 在一维结构中的位置，并创建相当长的金属阵列。 这项提案的具体目标是利用分子动力学模拟， 探索含金属的PNA双链体的结构。最近的分子 PNA-PNA和PNA-DNA双链体的动力学研究表明，PNA链保持 稳定的双螺旋结构。模拟开始于A-DNA或 B-DNA收敛到PNA结构，与报道的NMR结果一致 和晶体学观察。 核酸支架的初始坐标将从B-DNA中获得。 与P序列相同的典型双螺旋。 根据本发明，主链将被肽主链%2C替换。 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AMBER。力场 parm94将用先前确定的PNA参数进行补充 骨干已确定%5BPt（联吡啶）2%5D2%2B的坐标和电荷 由我们实验室的学生使用Gaussian98和B3LYP混合获得 功能和标准LANL2DZ基集。PNA原子的电荷也是 已经使用HF %2F6 - 31G%2A基组获得。 我们正在申请30%2C000服务单位的启动补助金， 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.