New methods for treating electrostatics and adaptive partitioning in QM/MM simulations

威斯康星州大学麦迪逊分校的Qiang Cui获得了理论、模型和计算方法项目的奖项，以开发用于生物和复杂化学系统的准确但有效的量子力学/分子力学（QM/MM）方法。PI和他的研究小组正在为采用有限球边界条件的QM/MM模拟寻求有效的静电处理，从而有助于将构型采样集中到活性位点，并使从头算QM/MM模拟具有成本效益。他们正在开发一种微观/介观模型，其中球形区域内的原子被原子化处理，而蛋白质的其余部分则由残余水平的可极化偶极子表示;本体溶剂是高斯场，相当于静态极限下的介电连续体。一个长期的目标是应用这种新的方法来确定分子因子，如金属分子伴侣和金属特异性转录因子系统中的过渡金属结合特异性。该方法也被应用于化学过程中，明确涉及许多水分子，无论是在本体溶液，空气/水界面或生物分子的内部。PI和他的研究小组开发的新的计算方法可以用来研究化学，生物学，医学和环境科学中的广泛的重要问题，目前很难或不可能研究。 这些理论/计算研究有可能在微观层面揭示令人惊讶的机制，帮助解释系统的宏观特征。 这些方法在流行的模拟包CHARMM中实现，并被其他科学团体广泛使用。

Qiang Cui of the University of Wisconsin, Madison is supported by an award from the Theory, Models and Computational Methods program to develop accurate but efficient quantum mechanics/molecular mechanics (QM/MM) methods for use in biological and complex chemical systems. The PI and his research group are pursuing effective electrostatic treatments for QM/MM simulations that employ finite sphere boundary conditions, thus helping to focus configurational sampling to the active site and making ab initio QM/MM simulations cost effective. They are developing a microscopic/mesoscopic model in which atoms within a spherical region are treated atomistically while the rest of the protein is represented by polarizable dipoles at the residue level; the bulk solvent is a Gaussian field, which is equivalent to a dielectric continuum in the static limit. One long term goal is to apply this new approach to identify molecular factors that dictate transition metal binding specificity in systems like metal chaperones and metal specific transcription factors. The methods are also being applied to chemical processes that explicitly involve many water molecules, either in bulk solution, the air/water interface or the interior of biomolecules.The novel computational methods that the PI and his research group develop may be used to study a broad range of important problems in chemistry, biology, medicine and environmental science that are currently difficult or impossible to study. These theoretical/computational studies have the potential to reveal surprising mechanisms at the microscopic level that help explain macroscopic features of the systems. These methods are implemented in the popular simulation package CHARMM and are widely used by other scientific groups.