NEW ALGORITHMS FOR INTRACTABLE DIRECT METHODS PROBLEMS

该项目确定了一些将用于 将直接相移方法的能力提高到更大的应用范围 比目前以常规方式确定的分子结构更多。 除了时间效率上的改进之外，还对一些计算 本建议书中描述的算法，将为您提供 关于如何获得更准确和更高分辨率的数据 可能有利于也可能不利于加强各种阶段性战略。 自然X射线数据将被记录和检查，以获得适当的基础 已解决的和未知的大分子结构来测试这些新的 方法：研究方法。计算机图形技术将在以下方面发挥重要作用 加强用于这些大分子的相变程序 将开发结构和图形软件，以帮助识别和 扩展存在于边缘相态电子中的结构模式 密度贴图。 在实验方面，初步研究表明，低温 对单个自然晶体的研究可以提供直接的相 之前被认为是无法获得的信息。一项分析 使用室温和液氮温度数据集， 记录于两种不同晶体的正交晶 结构，在两个不同的X射线衍射仪上测量，展示了 成功应用此方法所需的数据精度 不是不可逾越的。对几个难点结构的分析 此外，包括语法标识数据在内的确定表明， 只要付出最少的努力，就可以确保大块阶段的安全 只有十几个精挑细选和可识别的枢轴不变量 可以毫不含糊地确定结构解依赖于哪一个。 这些结果是一个令人鼓舞的迹象，表明复杂的晶体结构 含有多达300-500个原子的禁令被确定为含有更少的原子 比目前对于包含100个 原子或更少。

This project identifies a number of strategies that will be used to increase the power of direct phasing methods for applications to larger molecular structures than are currently determined in a routine fashion. In addition to the time efficient improvements to a number of computational algorithms described in this proposal, insights will be provided with regard to how the availability of more accurate and higher resolution data may or may not be advantageous to strengthening various phasing strategies. Native X-ray data will be recorded and examined for an appropriate base of both solved and unknown macromolecular structures to test these new methods. Computer graphics techniques will play an important role in strengthening the phasing procedures used for these large macromolecular structures and graphics software will be developed to help recognize and extend the structural patterns that exist in marginally phased electron density maps. On the experimental side, preliminary studies indicate that low temperature investigations of single native crystals can provide direct phase information that was previously thought to be unavailable. An analysis using a room temperature and a liquid nitrogen temperature data set, recorded from two different crystals of the orthorhombic gramicidin structure, measured on two different X-ray diffractometers, demonstrates that the precision required of the data to successfully apply this method is not insurmountable. Analysis of several difficult structure determinations, including that of the gramicidin data, moreover, shows that large blocks of phases can be secured with a minimum of effort provided that as few as a dozen well-chosen and identifiable pivotal invariants upon which the structure solution depends can be unambiguously determined. These results are an encouraging indication that complex crystal structures containing as many as 300-500 atoms ban be determined with far less difficulty than is currently experienced for structures containing 100 atoms or less.