Electronic Structure Theory: Algorithms, Applications and Cheminformatics

引言：目前还没有计算方法可以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。 该研究主要集中在开发新的和创新的方法进行电子结构计算。 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。 理论也应该足够简单，以提供对化学的洞察力。 电子结构理论：分子密度和分子径向密度（由我的小组定义）沿着它们的梯度和拉普拉斯算子，将被用来研究分子中原子和键的性质（ABIM）。 使用ABIM可以计算分子中给定原子或键的许多性质。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。 还将使用ABIM特性开发分子描述符。 这些将提供一套新颖的和有价值的相似性措施，用于药物设计等领域。将创建分子中原子（AIM）密度和径向密度的数据库，并开发使用这些AIM生成大分子密度或径向密度的方法。给定这些密度，我们将开发算法来使用整个大分子的密度进行构象能量搜索。 QM/AIM方法，其中分子被分成由AIM导出的密度描述的区域和较小的区域（例如，活性位点）使用波函数或密度泛函理论求解。 这种方法也可以用于模拟溶剂化。 一种电子结构理论，其中，不是将电子密度划分为原子贡献，而是使用变分方法从原子密度建立分子密度。可以可靠地预测相关能量的模型将基于可以容易地计算的属性来开发。 这些模型将帮助我们开发快速且适用于更大系统的复合方法，然后使用当前方法。 研究反应机理：我们将继续研究反应机理，特别是脱氨基和脱酰胺反应。 这些包括胞嘧啶、腺嘌呤、鸟嘌呤的脱氨基和谷氨酰胺的脱酰胺。 将研究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).