Electronic Structure Theory: Algorithms, Applications and Cheminformatics

目前还没有一种计算方法能够可靠地处理大分子或复杂的化学过程。合理的药物设计，新材料的合理设计，催化，溶液中的反应，大分子的激发态，表面化学和蛋白质折叠都是对计算化学家非常具有挑战性的问题的例子。研究的重点是发展新的和创新的方法来进行电子结构计算。长期目标是开发可靠的方法来处理非常大的分子，如蛋白质。这些理论也应该足够简单，以提供对化学的深入了解。***电子结构理论：分子密度和分子径向密度（由我的小组定义）以及它们的梯度和拉普拉斯函数，将用于研究分子中的原子和键（ABIM）的性质。使用ABIM可以计算与分子中给定原子或键相关的许多性质。这些研究将通过研究化学反应过程中化学键的变化，为化学键和结构反应性提供新的见解。分子描述符也将利用ABIM的性质来开发。这将为诸如药物设计等领域提供一套新颖而有价值的相似性测量方法。将建立分子内原子密度和径向密度数据库，并开发利用这些分子内原子密度产生大分子密度或径向密度的方法。考虑到这些密度，我们将开发算法来使用整个大分子的密度来执行构象能搜索。QM/AIM方法，其中分子分为由AIM衍生密度描述的区域和使用波函数或密度泛函数理论求解的较小区域（例如，活性位点）。这种方法也可用于模拟溶剂化。一种电子结构理论，它不是将电子密度划分为原子的贡献，而是使用变分方法从原子密度建立分子密度。能够可靠地预测相关能的模型将基于易于计算的性质来开发。这些模型将帮助我们开发复合方法，这些方法快速且适用于比当前方法大得多的系统。***研究反应机理：我们将继续研究反应机理，特别是脱氨和脱酰胺反应。这些包括胞嘧啶、腺嘌呤、鸟嘌呤的脱胺和谷氨酰胺的脱胺。研究了溶剂和催化剂的作用。在我们的研究中，我们将应用上述方法来深入了解这些反应。这些反应在诱变、致癌和高氨血症（谷氨酰胺）中很重要

Introduction: No computational methodologies currently exist that can deal reliably with macromolecules or complex chemical process. Rational drug-design, rational design of new materials, catalysis, reactions in solution, excited states of large molecules, surface chemistry, and protein folding are all examples of problems that are very challenging to computational chemists. The research focuses broadly on the development of novel and innovative methods for preforming electronic structure calculations. The long-term goal is to develop reliable methodologies for dealing with very large molecules, such as proteins. The theories should also be simple enough to provide insight into the chemistry. ***Electronic Structure Theory: The molecular density and the molecular radial density (defined by my group) along with their gradient and Laplacian, will be used to study the properties of both Atoms and Bonds In Molecules (ABIM). With ABIM it is possible to compute a number of properties associated with a given atom or bond in a molecule. Such studies will provide new insight into chemical bonding and structure-reactivity by studying the change in chemical bonds during a chemical reaction. Molecular descriptors will also be developed using the ABIM properties. These will provide a novel and valuable set of similarity measures for use in areas such as drug design. A database of Atoms-In-Molecules (AIM) densities and radial densities will be created and methods will be developed to use these AIM to generate the density, or radial density, of macromolecules. Given these densities, we will develop algorithms to perform conformational energy searches using the density of the entire macromolecule. A QM/AIM approach, in which the molecule is divided into a region described by AIM derived densities and a smaller region (e.g., the active site) is solved using wavefunction or density functional theory. Such an approach may also be useful in modelling solvation. An electronic structure theory in which, instead of partitioning the electronic density into atomic contributions, the molecular density will be built from atomic densities using a variational approach. Models which can reliably predict the correlation energy will be developed based on properties that can be easily calculated. These models will help us develop composite methods that are fast and applicable to much larger systems then with the current methods. ***Investigating Reaction Mechanisms: We will continue investigating reaction mechanisms, especially deamination and deamidation reactions. These include the deamination of cytosine, adenine, guanine and the deamidation of glutamine. The role of solvent and catalysts will be investigated. In our studies we will apply the methodologies described above to provide insight into these reactions. These reactions are important in mutagenesis, carcinogenesis and hyperammonemia (glutamine).**