Theoretical Modeling of the Vibrational Spectroscopy of Nucleic Acids

项目摘要/摘要 核苷酸和它们的环境之间的相互作用是决定 核酸的识别和配对，这与它们的传播能力密切相关 并维护遗传信息的完整性。线性和超快振动光谱是 是探索这些相互作用和揭示核酸分子机制的有力工具 在广泛的时间范围内具有键特定结构分辨率的杂交。尽管 它们的重要性，实验光谱通常是高度拥挤的，一般规则是 准确地将复杂的光谱特征分配给潜在的结构和动力学 目前还不能获得核酸。 拟议研究的目标是开发一个理论框架，以准确地 并有效地计算了核酸在碱式羰基伸缩中的振动光谱 从而建立结构-光谱关系并阐明其作用机理和作用机制。 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，直接从站点频率生成瞬时频率 分子动力学(MD)模拟。目标2是建立耦合方案来模拟 生色团之间的相互作用。在建立理论框架后，目标3是 将MD模拟和理论光谱建模相结合，对 DNA和RNA寡核苷酸建立结构-光谱关系，并研究 DNA寡核苷酸在水溶液和膜表面的杂交。 拟议的研究将提供一个新的理论框架，可以很容易地应用于 模拟各种线性和非线性振动光谱，特别是二维振动光谱 红外和和频产生光谱学。此方法提供了一种实用的方法来 桥梁MD模拟和光谱实验，这使得能够解释 分子水平上的复杂实验光谱。结合原子MD模拟和 理论光谱学建模，提出的研究将阐明其机理和关键 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，以在时间上和 在空间上控制这些过程，以应用于基于DNA的技术。 。

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. .