Incorporating MM Polarization in hybrid QM/MM calculations

计算机模拟现在在理解生物系统和设计分子作为新材料和新药物方面发挥着重要作用。在某些情况下，重要的是要在原子水平上研究分子的细节，以便了解分子内电子的分布，那么量子力学就是首选的方法。在这些分子周围的环境影响电子分布的情况下，则使用混合量子力学/分子力学（QM/MM）方法。QM意味着可以精确地研究感兴趣的分子；MM意味着分子所处的环境也可以考虑在内，尽管精度较低。在这些计算的MM部分中，假设电子具有固定的分布，不随感兴趣的QM区域的响应而变化。在这里，我们建议引入新的计算机方法，以便考虑MM区域内电子分布的极化。一个简单的例子就能突出这个效果的重要性。当药物与酶结合时，药物和酶的结构必须弯曲以适应彼此。在电子的空间分布中也出现了类似的调节。因此，忽略这种再分配（即两极分化）就像试图戴上几乎凝固的手套一样。该项目的一个重要部分将包括确保这些方法可以很容易地被其他科学家使用的工作。这种新方法的应用将增加对生物过程的原子和分子水平的理解。受益的科学家不仅包括理论家，还包括酶学家、参与药物设计的科学家、生物无机化学家、光化学家、材料科学家、植物科学家、光谱学家以及参与生物技术软件公司的科学家。

Computer simulation now plays a major role in understanding biological systems and in the design of molecules as new materials and new pharmaceuticals. In cases where it is important to study the molecules in atomic-level detail so that the distribution of electrons within the molecules can be understood, then quantum mechanics is the method of choice. In cases where the environment surrounding these molecules affects this distribution of electrons, then hybrid quantum mechanical / molecular mechanics (QM/MM) methods are used. The QM means that the molecule of interest can be studied accurately; the MM means that the environment that this molecule is in can also be taken into account, albeit at a lower level of accuracy. Within the MM part of these calculations, it is assumed that the electrons have a fixed distribution that does not change in response to the QM region of interest. Here we propose to introduce new computer methods so that the polarization of the electron distribution within the MM region can be taken into account. A simple illustration should highlight the importance of this effect. When a drug binds to an enzyme, the structure of both the drug and the enzyme must flex to accommodate each other. A similar accommodation is occurring in the spatial distribution of the electrons. Ignoring this redistribution (i.e. polarization) is therefore rather like attempting to put on a glove that is almost frozen solid. A significant part of the project will involve work to ensure that these methods can be readily used by other scientists. Applications of this new method will enable increased atomic and molecular level understanding of biological processes. The scientists that will benefit will not only include theoreticians but also enzymologists, those involved in drug design, bioinorganic chemists, photochemists, material scientists, plant scientists, spectroscopists, and those involved in biotechnology software companies.