"Low-Resolution Interiors & Interfaces Can Achieve High-Resolution Accuracy"

描述（由申请人提供）：建议假设是即使在低分辨率下，我们也可以找到并鉴定正确的结构模型，其将良好的全原子堆积与松弛的局部构象相结合，从而具有高分辨率结构解的准确性。要解决的问题是，生物学上重要的蛋白质和核酸的大型复合物只能产生低分辨率（3分或更低）的衍射数据，其中原子间接触的功能关键细节不能直接看到，甚至整体折叠模式也变得不确定。我们开发并在更高分辨率下成功应用的诊断和校正方法极其敏感，可以识别具有高分辨率有效性的模型，并基本上拒绝任何与此不正确的偏离。然而，这是一个非常困难的，目前尚未解决的搜索问题，以确定这样的模型。因此，本提案的主旨是为这项任务制定和测试搜索程序，并确定解决方案的独特性。这些想法与标准范式相矛盾，提出即使在低分辨率下也可以有效地使用晶体学上不可见的氢原子，只有一小部分模型与密度和已知的分子性质相容，因此即使在低分辨率下也可以实现详细的准确性。

DESCRIPTION (provided by applicant): The proposal hypothesis is that even at low resolution, we can find and identify the correct structure model that combines good all-atom packing with relaxed local conformations and thus has the accuracy of a high- resolution structure solution. The problem to be solved is that biologically important large complexes of proteins and nucleic acids yield diffraction data only to low resolution (3¿ or worse), where functionally critical details of interatomic contacts cannot be seen directly and even overall folding patterns become uncertain. The diagnosis and correction methods we developed and applied successfully at higher resolution are extremely sensitive and can recognize a model with high-resolution validity and reject essentially any incorrect departure from that. However, it is a very difficult and currently unsolved search problem to identify such a model. The thrust of this proposal is therefore to develop and test search procedures for this task and determine the uniqueness of the solutions. These ideas contradict the standard paradigm by proposing that the crystallographically invisible hydrogen atoms can be effectively used even at low resolution, that only a small range of models are compatible both with the density and with known molecular properties, and therefore that detailed accuracy might actually be attainable even at low resolution.