Density Functional Theory for van der Waals Interactions

描述(申请人提供)：Q-Chem是一个最先进的商业量子化学程序，用于对包括生物、化学和材料科学在内的广泛学科的原子和分子过程进行建模。在量子化学方法中，密度泛函理论(DFT)可能是应用最广泛的，特别是在分子生物学中，因为它能够以合理的计算代价精确地模拟广泛的分子体系。尽管DFT被广泛使用，但它不包括色散关联效应或van der Waals相互作用，后者在确定分子体系的整体构象中起着关键作用，因此在DNA和蛋白质、分子识别、晶体堆积等研究中是必不可少的。在本项目的第一阶段，我们为密度泛函色散模型XDM开发了一个有效的自洽会函数和核梯度解，并证明了它纠正了目前DFT方法在结构和能量研究中的一些失败。在这个第二阶段的提案中，我们计划将XDM模型的色散纳入DFT应用的所有主要方面，包括基态和激发电子态的能量和结构计算，并进一步提高精度。为了证明DFT-XDM方法在模拟具有生物学意义的系统方面的有效性，我们将研究两个具有挑战性的分子过程，即顺铂与DNA的结合过程和光活性黄色蛋白(PYP)中的电子跃迁。顺铂被广泛应用于化疗，而光活性黄蛋白是一种被广泛研究的光感受器，是理解信号转导的关键。正如我们将展示的，这里提出的DFT-XDM模型的成功开发和实施将导致更精确的DFT解决方案。 公共卫生相关性：该项目旨在开发和实施一种非常准确的DFT方法。离散傅立叶变换是分子模拟的核心，在生物研究和药物开发中得到了广泛的应用。改进后的离散傅里叶变换将显著提高研究人员的工作质量，扩大离散傅里叶变换的应用范围。

DESCRIPTION (provided by applicant): Q-Chem is a state-of-the-art commercial quantum chemistry program that is used to model atomic and molecular processes over a wide range of disciplines, including biology, chemistry, and materials science. Among the quantum chemistry methods, density functional theory (DFT) is perhaps the most widely used, especially in molecular biology, due to its ability to accurately model a wide range of molecular systems with reasonable computational cost. Despite its wide use, DFT does not include the dispersion correlation effect, or van der Waals interaction, which plays a critical role in the determination of the overall conformations of molecular systems and accordingly, is indispensable in the study of DNA and proteins, molecular recognition, the packing of crystals, etc. In Phase I of this project, we developed an efficient SCF and nuclear gradient solution for a density functional dispersion model called XDM, and demonstrated that it corrected some of the failures of current DFT methods in structural and energetic studies. In this Phase II proposal, we plan to incorporate dispersion of the XDM model into all the major aspects of DFT applications, including energetic and structural calculations of both ground and excited electronic states, with further improved accuracy. To demonstrate the utility of the DFT-XDM approach for modeling systems of biological interest, we will investigate two challenging molecular processes, namely the binding process of cisplatin to DNA, and electronic transitions in photoactive yellow protein (PYP). Cisplatin is widely used in chemotherapy, and photoactive yellow protein is a widely studied photoreceptor that is key to understanding signal transduction. As we will show, the successful development and implementation of the DFT-XDM model proposed here will lead to much more accurate DFT solutions. PUBLIC HEALTH RELEVANCE: This project aims to develop and implement a very accurate DFT method. DFT is at the core of molecular modeling and is applied widely in biological research/development and in drug discovery. The improved DFT will significantly increase researchers' quality of work and extend the application scope of DFT.