MOLECULAR DYNAMICS SIMULATIONS OF METAL-CONTAINING MODIFIED PNA DUPLEXES

含金属改性 PNA 双链体的分子动力学模拟

• 批准号: 7723168
• 负责人: Catalina Achim
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723168
• 关键词: A-Form DNA; Affinity; Agreement; Amber; B-DNA; Base Pairing; Benchmarking; Binding; Biological; Charge; Complement; Computer Retrieval of Information on Scientific Projects Database; Computer software; Computers; DNA; Devices; Dimensions; Electronics; Funding; Genetic Code; Goals; Grant; Helix (Snails); Hybrids; Hydrogen; Hydrogen Bonding; Institution; Ions; Length; Ligands; Location; Metals; Methods; Molecular; Nanostructures; Nucleic Acids; Object Attachment; Peptide Nucleic Acids; Peptides; Positioning Attribute; Property; RNA; Reporting; Research; Research Personnel; Resources; Services; Source; Standards of Weights and Measures; Structure; Students; Sugar Phosphates; Time; United States National Institutes of Health; Vertebral column; analog; base; ear helix; molecular dynamics; nanometer; nanosized; nucleic acid structure; scaffold; simulation

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 肽核酸（PNA）是DNA的合成类似物，其中包含相同 核仁酶是DNA中的核碱酶，但磷酸糖被A取代 结构上同型假肽链。 沃森·克里克（Watson Crick）的PNA形式 基本的双链体，与DNA同性形成。 PNA链可以结合 到其他PNA链％2C到DNA和RNA。 此要求的计算机时间 应用将用于研究含金属的替代碱基对 可以在PNA中引入。对这些替代底部的追求 生物学相关性，因为它将提供有关评估的信息 这些基础底座的潜力通过使用协调键存储信息 而不是以类似于遗传密码的方式而不是氢键％2C。 另外，新的混合PNA - 金属分子具有可以是 用于分子电子应用。 分子的主要推力 电子设备是发现具有纳米尺寸的新分子的发现 可以用作分子电线或设备以及用于组装的方法 纳米级电路中的分子。 我们发现肽核酸（PNA）％2C a的合成类似物的合成类似物 DNA％2C可以用核碱基用作金属离子的支架 在PNA低聚物中，配体赋予金属离子高亲和力 PNA双链体。 结果，修饰的复式由A桥 氢和协调键的组合。 我们将此策略用于 基于含有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 并入复合物，使我们能够将TM离子放在特定的 位于1-D结构中的位置，并创建相当长的金属阵列。 该提案的具体目标是使用分子动力学模拟 探索含金属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链维持 稳定的双螺旋结构。模拟从A-DNA或 B-DNA收敛到与报道NMR相吻合的PNA结构 和晶体学观察。 核酸支架的初始坐标将从B-DNA获得 规范双螺旋​​具有与P相同的P。糖磷酸盐 骨干将根据肽骨架％2C代替 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 PARM94将与先前确定的PNA参数相辅相成 骨干。 ％5BPT（Bypridine）2％5D2％2B的坐标和费用 由我们实验室的学生使用Gaussian98与B3Lyp混合动力车获得 功能和标准LANL2DZ基集。 PNA原子的费用也是 已经使用HF％2F6-31G％2A基集获得了。 我们要求BEN的30％2C000服务单元的首发赠款以启动 模拟并获得基准。