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

威斯康星大学麦迪逊分校的Qiang Cui获得了理论、模型和计算方法项目的奖励，以开发用于生物和复杂化学系统的精确而高效的量子力学/分子力学（QM/MM）方法。PI和他的研究小组正在为采用有限球体边界条件的QM/MM模拟寻求有效的静电处理，从而有助于将配置采样集中到活性部位，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馀水平的极化偶极子表示；体溶剂为高斯场，相当于静态极限下的介电连续体。一个长期目标是应用这种新方法来鉴定在诸如金属伴侣和金属特异性转录因子等系统中决定过渡金属结合特异性的分子因子。这些方法也被应用于明确涉及许多水分子的化学过程，无论是在散装溶液中，空气/水界面还是生物分子的内部。PI和他的研究小组开发的新型计算方法可用于研究化学，生物学，医学和环境科学中目前难以或不可能研究的广泛重要问题。这些理论/计算研究有可能揭示微观层面上令人惊讶的机制，帮助解释系统的宏观特征。这些方法在流行的仿真包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.