Incorporating MM Polarization in hybrid QM/MM calculations

点击翻译按钮获取中文摘要

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.