Accurate Atomistic Modeling of Solutions

阿肯色大学的Peter Pulay获得了化学理论、模型和计算方法项目的奖励，以开发改进的电子结构方法来模拟溶液中的反应，并可能扩展到蛋白质环境。这些反应的精确模拟需要热力学平均值的评估，这增加了许多数量级的计算负担。Pulay最近提出的通用极化量子力学/分子力学（GP-QM/MM）方法已经在Metropolis蒙特卡罗代码中实现，并显示出在几乎没有牺牲精度的情况下，将传统的QM/MM计算速度提高了四个数量级。Pulay和他的同事将为新方法开发分析梯度，以确定溶液中的反应路径。他们还将实施改进的溶剂模型，以匹配反应系统描述的准确性。他们将把目前的蒙特卡罗模拟扩展到另一种分子动力学方法，这种方法可以提供有关变化的时间尺度的信息。新技术将应用于预测pKa值，两性离子和中性形式的氨基酸和小肽之间的平衡，肽的构象偏好，以及已知受极性溶剂强烈影响的反应。他们还将研究决定阴离子是否优先吸附在水微滴表面的因素。在过去的三十年里，计算机能力和理论方法都取得了巨大的进步，终于可以对中等规模的气相化学体系的电子结构和性质进行精确的常规计算。然而，大多数化学（以及几乎所有的生物化学）都是在溶液或蛋白质环境中发生的。像水这样的极性溶剂对化学反应性有深远的影响，需要大量的模拟运行才能获得准确的平均值。因此，在方法中经常进行重要的近似，尽管这降低了它们的准确性。相反，Pulary小组正在开发的方法旨在纠正这种情况，并已被证明可以将计算成本降低4个数量级；对于更大的系统，预计会节省更多的费用。这将允许使用精确的理论方法来解决问题。普拉伊在电子结构理论领域贡献了许多算法的进步，从分析梯度技术开始，这是当前大多数量子化学应用的基石。其他广泛使用的贡献是分子几何优化，加速计算波函数（SCF）的基本方法，核磁共振化学位移的计算和局部电子相关。Pulay和他的同事们还致力于利用计算机模拟分子来改善本科和研究生的化学教育，使用复杂的计算机图形来传达信息。

Peter Pulay of the University of Arkansas is supported by an award from the Chemical Theory, Models and Computational Methods program to develop improved electronic structure methods for simulating reactions in solutions, with possible extension to a protein environment. Accurate simulation of these reactions requires the evaluation of thermodynamic averages, increasing the computational burden by many orders of magnitude. Pulay's recent General Polarizability Quantum Mechanics / Molecular Mechanics (GP-QM/MM) methodology has already been implemented in a Metropolis Monte Carlo code and shown to speed up conventional QM/MM calculations by four orders of magnitude with barely any sacrifice in accuracy. Pulay and his coworkers will develop analytical gradients for the new method, allowing the determination of reaction paths in solutions. They will also implement improved solvent models, to match the accuracy of the description of the reactive system. They will extend the current Monte Carlo simulations to the alternative Molecular Dynamics method which can supply information about the time scale of the changes. The new techniques will be applied to the prediction of pKa values, equilibria between zwitterionic and neutral forms of amino acids and small peptides, conformational preferences of peptides, and reactions known to be strongly affected by polar solvents. They will also investigate the factors determining whether anions preferentially adsorb on the surface in water microdroplets.During the last three decades, both computer power and theoretical methods advanced tremendously, finally allowing accurate routine calculation of the electronic structures and properties of medium-sized chemical systems in the gas phase. However, most chemistry (and virtually all biochemistry) takes place in solution or in a protein environment. Polar solvents like water have a profound effect on chemical reactivity, and require very large numbers of simulation runs to obtain accurate averages. As a result, significant approximations are frequently made in the methods, although this reduces their accuracy. Instead, the methods under development in the Pulary group aim to correct this situation and have been shown to reduce the computational cost by 4 orders of magnitude; larger savings are expected for bigger systems. This will allow the use of accurate theoretical methods for solutions. Pulay has contributed a number of algorithmic advances in the field of electronic structure theory, beginning with the analytical gradient technique which is the cornerstone of most current quantum chemical applications. Other widely used contributions are molecular geometry optimization, acceleration of the basic method to calculate wavefunctions (SCF), the calculation of NMR chemical shifts, and Local Electron Correlation. Pulay and his coworkers also work on utilizing computer simulation of molecules to improve undergraduate and graduate chemistry education, using sophisticated computer graphics to convey the information.