Simulation of the Interaction of DS DN/PNA

DS DN/PNA 相互作用的模拟

• 批准号: 6766476
• 负责人: YASUYUKI ISHIKAWA
• 金额: $ 3.5万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766476
• 关键词: DNA; alkanes; atomic force microscopy; charge transfer complex; chemical models; computer simulation; conformation; electrical property; electrochemistry; intermolecular interaction; microarray technology; model design /development; molecular dynamics; nanotechnology; nucleic acid hybridization; peptide nucleic acids; statistics /biometry; structural biology

The goal of this pilot project is to develop and apply theoretical chemical methods of simulating the stable conformations of nanometer-sized DNA with PNA with and without single-base mismatches, and of double-stranded DNA/PNA with an alkanethiol monolayer. The simulation project is part of a pair of studies aimed at developing a DNA nanoarray chip to enhance the speed and lower the cost of analyzing for gene variations or patterns. The associated pilot project is experimental, with the goals of fabrication and detection of nanopattern DNA arrays. Simulating the underlying mechanism of molecular interactions is needed: (1) to understand the basic charge transport properties of DNA/PNA in an electrochemical environment, and (2) to predict the forces characteristic of single-base mismatches in DNA/PNA to interpret experimental atom force microscopic (AFM) measurements of the arrays. Three aspects of simulating the systems under consideration need to be addressed. First the stable conformations of DNA/PNA with and without DNA mismatches need to be examined. The replica exchange Monte Carlo (REMC) method is well suited to identifying multiple low-energy configurations of complex systems. Molecular dynamics (MD) simulation will also be employed to determine the mechanism of hybridization. The second aspect to be considered will go beyond electronic effects to include internal vibrations of individual molecules and tribological effects in MD simulations. This extension is necessary to account for effects arising from kinks and gauche defects on the interaction of DNA/PNA with an alkanethiol monolayer when the former is indented into the latter in the course of AFM measurements. A third aspect to be considered arises from the need to understand charge transport properties that govern DNA/PNA in an electrochemical environment. This task requires a combination of MD with a molecular orbital method. The fragment molecular orbital (FMO) method is applicable to very large systems. It will be incorporated into an MD algorithm to create a direct FMO MD routine that will be used to examine the underlying mechanism that accounts for the high sensitivity of electrochemical detection to single-base mismatches.

该试点项目的目标是开发和应用理论化学方法来模拟具有或不具有单碱基错配的 PNA 的纳米级 DNA 以及具有烷硫醇单层的双链 DNA/PNA 的稳定构象。该模拟项目是两项研究的一部分，旨在开发 DNA 纳米阵列芯片，以提高基因变异或模式的分析速度并降低成本。相关的试点项目是实验性的，目标是制造和检测纳米图案 DNA 阵列。需要模拟分子相互作用的基本机制：(1) 了解电化学环境中 DNA/PNA 的基本电荷传输特性，以及 (2) 预测 DNA/PNA 中单碱基错配的力特征以解释实验结果阵列的原子力显微镜（AFM）测量。 需要解决所考虑的系统仿真的三个方面。首先需要检查有或没有 DNA 错配的 DNA/PNA 的稳定构象。副本交换蒙特卡罗 (REMC) 方法非常适合识别复杂系统的多个低能量配置。分子动力学（MD）模拟也将用于确定杂交机制。要考虑的第二个方面将超越电子效应，包括单个分子的内部振动和 MD 模拟中的摩擦学效应。当 DNA/PNA 在 AFM 测量过程中缩进到后者中时，这种扩展对于考虑扭结和稀疏缺陷对 DNA/PNA 与烷硫醇单层相互作用产生的影响是必要的。要考虑的第三个方面是需要了解控制 DNA/PNA 的电荷传输特性。 电化学环境。该任务需要将MD与分子轨道方法相结合。碎片分子轨道（FMO）方法适用于非常大的系统。它将被纳入 MD 算法中，以创建直接的 FMO MD 例程，该例程将用于检查解释电化学检测对单碱基错配的高灵敏度的潜在机制。