A NEW SOFTWARE FOR FINE SLICE DATA COLLECTION

用于精细切片数据采集的新软件

• 批准号: 6394726
• 负责人: RONALD C HAMLIN
• 金额: $ 19.61万
• 依托单位: AREA DETECTOR SYSTEMS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-22 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394726
• 关键词: X ray crystallography; bioimaging /biomedical imaging; computer program /software; computer system design /evaluation; data collection methodology /evaluation; method development; sectioning

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.

该项目的目标是编写一个新的软件包来处理通过精细切片方法收集的蛋白质晶体学数据。在该方法中，每帧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。这与标准旋转方法形成对比，在标准旋转方法中，晶体会以每帧 10 度范围内的更大角度旋转。精细切片方法将产生更好质量的数据，因为它在每次反射顶部的背景量最少。然而，该软件将更加复杂，因为每个反射强度将分散在许多火焰中（在标准旋转方法中只会分散到 1 或 2 个火焰）。我们在第一阶段非常成功。首先，我们能够为精细切片方法开发一个初步但完整的软件包。该软件包含许多新想法，并产生具有低 R[sym] 值的良好数据。此外，我们还发现了一种新方法，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团体作为联系人，然后作为测试站点来广泛测试和完善新软件包。在第二阶段结束时，经过全面测试后，新软件包将以较低的名义费用进行分发。该新软件将提高蛋白质晶体学数据质量，从而获得更好的蛋白质三维结构。这些结构现在如此重要，因为它们不仅用于进一步了解分子生物学，还用于合理设计新药物。新型HIV蛋白酶抑制剂现在可以控制大多数患者的艾滋病疾病，这证明了这种药物设计方法的成功。拟议的商业应用：市场虽小，但蛋白质晶体学界真正需要的产品。它可以极大地帮助药物设计过程。