Theoretical Modeling of the Vibrational Spectroscopy of Nucleic Acids

核酸振动光谱的理论模型

基本信息

批准号：
10330456
负责人：
Lu Wang
金额：
$ 15.37万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2025-01-31
项目状态：
未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Interactions between nucleotides and their environment are essential in determining the recognition and pairing of nucleic acids, which are intimately connected to their ability to transmit and maintain the integrity of genetic information. Linear and ultrafast vibrational spectroscopy is a powerful tool to probe these interactions and reveal the molecular mechanism of nucleic acids hybridization with bond-specific structural resolution over a wide range of time scales. Despite their importance, experimental spectra are usually highly congested and a general rule that accurately assigns the complex spectral features to the underlying structure and dynamics of nucleic acids is currently not available. The objectives of the proposed research are to develop a theoretical framework that accurately and efficiently calculates the vibrational spectra of nucleic acids in the base carbonyl stretch region, and thereby to establish a structure-spectrum relation and elucidate the mechanism and key interactions in the hybridization of DNA oligonucleotides. Aim 1 supports the objectives by developing a frequency map that generates instantaneous site frequencies directly from molecular dynamics (MD) simulations. Aim 2 is to establish coupling schemes that model the interactions between chromophores. Upon building the theoretical framework, Aim 3 is to combine MD simulations and theoretical spectroscopy modeling and perform a systemic study of DNA and RNA oligonucleotides to build a structure-spectrum relation and to investigate the hybridization of DNA oligonucleotides in aqueous solution and on membrane surfaces. The proposed research will provide a novel theoretical framework that can be readily applied to model a variety of linear and non-linear vibrational spectroscopy, in particular two-dimensional infrared and sum-frequency generation spectroscopy. This approach provides a practical way to bridge MD simulations and spectroscopy experiments, which enables the interpretation of the complex experimental spectra at the molecular level. Combining atomistic MD simulations and theoretical spectroscopy modeling, the proposed research will elucidate the mechanism and key interactions in the molecular recognition and pairing of complementary DNA and RNA strands, which will guide the design of new vibrational spectroscopy experiments to temporally and spatially control these processes for applications in DNA-based technology. .

项目概要/摘要核苷酸与其环境之间的相互作用对于确定核酸的识别和配对，这与其传播能力密切相关并保持遗传信息的完整性。线性和超快振动光谱是探测这些相互作用并揭示核酸分子机制的强大工具在广泛的时间尺度上具有键特异性结构分辨率的杂交。尽管考虑到它们的重要性，实验光谱通常是高度拥挤的，并且一般规则是准确地将复杂的光谱特征分配给底层结构和动力学目前尚无核酸。拟议研究的目标是开发一个理论框架，准确地并有效计算碱基羰基链中核酸的振动光谱区，从而建立结构-谱关系并阐明其机制和 DNA寡核苷酸杂交中的关键相互作用。目标 1 通过以下方式支持目标：开发一个频率图，直接从分子动力学（MD）模拟。目标 2 是建立耦合方案来建模发色团之间的相互作用。在建立理论框架后，目标 3 是结合 MD 模拟和理论光谱建模，并对 DNA 和 RNA 寡核苷酸建立结构-谱关系并研究 DNA 寡核苷酸在水溶液中和膜表面上的杂交。拟议的研究将提供一个新颖的理论框架，可以很容易地应用于模拟各种线性和非线性振动光谱，特别是二维红外和和频发生光谱。这种方法提供了一种实用的方法桥接 MD 模拟和光谱实验，从而能够解释分子水平上的复杂实验光谱。结合原子 MD 模拟和理论光谱建模，所提出的研究将阐明其机制和关键互补 DNA 和 RNA 链的分子识别和配对中的相互作用，这将指导新的振动光谱实验的设计空间控制这些过程以应用于基于 DNA 的技术。。