Crystallographic Structure Determination/Refinement Using Atomic Electron Density Functions, and Optimization of Appropriate Force Fields for Analysis

该项目将开发(1)促进大分子结构确定并提高其准确性的方法，以及(2)确定适用于预测蛋白质和病毒已知结构变体的力场参数的方法。这些改进晶体结构测定的努力的核心是开发一种方法来快速计算原子的预期电子密度，这种方法首次完全解释了实验的分辨率极限。优化模型与实验电子密度一致性的改进方法将得到进一步发展。电子密度函数也将被应用于摇晃烘焙直接相测定方法中试验原子的放置。真实空间精化的发展将导致对原子结构的更精确的描述。对力场的研究将使对修改对结构的影响的预测更加可靠。综上所述，这些进展将极大地促进确定哪些原子相互作用对许多系统中的催化、特异性和其他功能至关重要。

This project will develop (1) methods to facilitate macromolecular structure determination and improve its accuracy, and, (2) methods to determine force field parameters appropriate for prediction of variants of known structure of proteins and viruses. Central to these efforts to improve crystallographic structure determination is exploitation of a method to quickly calculate the expected electron density of an atom in a way that for the first time accounts fully for the resolution limit of the experiment. Refinement methods that optimize the agreement between model and experimental electron density will be developed further. The electron density function will also be applied to the placement of trial atoms in the Shake-and-Bake direct method of phase determination. The development of real-space refinement will lead to a more precise description of atomic structure. The research into force fields will allow much more reliable prediction of the effects of modifications upon structure. Together, these advances will greatly facilitate the determination of which atomic interactions are critical for catalysis, specificity and for other functions in many systems.