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: 6540630
• 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 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540630
• 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.

本计画的目标是编写一个新的软体套件来处理蛋白质晶体学的数据，这些数据是以精细切片法收集。在这种方法中，X射线衍射的每个帧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。这是为了与标准旋转方法形成对比，在标准旋转方法中，晶体将旋转每帧10 °范围内的较大角度。精细切片方法将产生更好质量的数据，因为它将具有落在每个反射顶部的最小量的背景。然而，软件将更加复杂，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，它将仅展开到1或2个火焰）。我们在第一阶段非常成功。首先，我们能够开发一个初步的，但完整的软件包的精细切片方法。该软件包含许多新的想法，并产生良好的数据与低R[sym]值。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团体作为联系人，并在以后作为测试站点，对新软件包进行广泛的测试和改进。在第二阶段结束时，经过彻底测试后，新的软件包将以低象征性收费分发。这款新软件将提高蛋白质晶体学数据的质量，从而获得更好的蛋白质三维结构。这些结构现在非常重要，因为它们不仅用于进一步理解分子生物学，而且用于合理设计新药。新的HIV蛋白酶抑制剂现在可以控制大多数患者的艾滋病疾病，这是这种药物设计方法成功的证明。拟议的商业应用：市场小，但产品确实需要蛋白质晶体学社区。它可以大大帮助药物设计过程。