A NEW SOFTWARE FOR FINE SLICE DATA COLLECTION

本项目的目标是编写一个新的软件包，用于处理用精细切片方法收集的蛋白质结晶学数据。在这种方法中，每一帧X射线衍射都是在晶体旋转非常小的角度(例如0.10(或更小))的情况下收集的。这与标准的旋转方法形成了对比，在标准的旋转方法中，晶体将在每帧10的范围内旋转更大的角度。精细切片方法将产生质量更好的数据，因为它将具有落在每个反射上的最小数量的背景。然而，软件会复杂得多，因为每个反射强度将在许多火焰中展开(在标准旋转方法中，它只会展开到1到2个火焰)。我们在第一阶段非常成功。首先，我们能够为Fine Slice方法开发一个初步的、但完整的软件包。该软件包含了许多新的思想，产生了R[sym]值低的良好数据。此外，我们还发现了一种新的方法，可以自动解决索引问题。在第二阶段，我们希望使用至少四个外部小组作为联系人和稍后的测试版站点来广泛测试和改进新的软件包。在第二阶段结束并经过彻底测试后，新的软件包将以较低的名义费用分发。这一新软件将提高蛋白质结晶学数据的质量，从而获得更好的蛋白质三维结构。这些结构现在如此重要，因为它们不仅被用来进一步了解分子生物学，而且还被用来合理地设计新药。新的HIV蛋白水解酶抑制剂现在可以控制大多数患者的艾滋病疾病，是这种药物设计方法成功的证明。建议的商业应用：市场很小，但产品是蛋白质结晶界真正需要的。这对药物设计过程有很大的帮助。

The goal of this project is to write a new software package to process data for Protein Crystallography collected with the fine slice method. In this method, each frame of x-ray diffraction is collected with the crystal rotated by a very small angle, for example 0.10 (or smaller). This is to contrast with the standard rotation method where the crystal would rotate by a larger angle in the range of 10 per frame. The fine slice method would yield a better quality data since it would have the smallest amount of background falling on top of each reflection. However, the software will be much more complex since each reflection intensity will be spread out in many flames (it would only be spread out to 1 or 2 flames in a Standard rotation method). We were very successful in the Phase I period. First, we were able to develop a preliminary, but complete software package for the Fine Slice Method. This software contains many new ideas and yields good data with low R[sym] value. In addition, we have discovered a new method that would solve the indexing problem in an automatic way. During Phase II, we would like to extensively test and refine the new software package using at least four outside groups as contacts and, later on, as beta sites. At the end of the Phase II period and after being thoroughly tested, the new software package will be distributed at a low nominal charge. This new software will enhance the protein crystallography data quality which will result in better three dimensional structure of proteins. These structures are now so important because they are used not only to further understand Molecular Biology but also to rationally design new drugs. New HIV protease inhibitors which now can control AIDs disease in most patients are the testimonies of the success of this drug design method. PROPOSED COMMERCIAL APPLICATIONS: Small market but product really needed by protein crystallography community. It could greatly help in drug design procedure.