应用分子置换法确定相位和解析蛋白质晶体结构

项目名称： 应用分子置换法确定相位和解析蛋白质晶体结构

项目编号： No.10874229

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 电工技术

项目作者： 江凡

作者单位： 中国科学院物理研究所

项目金额： 45万元

中文摘要： 在获得此项目资助之前，我们提出一个新的计算分子置换法的旋转函数的方法。此项目的研究目标就是发展一套新的分子置换法（MR）。它的特点是应用帕特森矢量和可以使用小片段肽链从头计算相位。这是因为帕特森矢量在某些情况下更加灵敏。目前，相关的计算软件已经基本完成，而且较之前的版本速度提高了近十倍。软件名称是PVMR。PVMR通过组装MR单片段肽链的解，得到较大的多片段的MR解，并在蛋白质结构数据库中搜寻相似结构域。这些相似结构域可以作为下一步进行常规的MR解析的模型。发现这一策略可行，所以我们实际上是发展了一个从头计算MR解的方法，因为它不依赖蛋白质的序列相似性选择搜索模型。介绍完整的PVMR的计算方法和初步测试结果发表在国际晶体学会的期刊（ACTA）上，当年影响因子近50，超过《自然》和《科学》。

中文关键词： 分子置换法；相关系数；全局搜索；适应度；相似结构域

英文摘要： Before the support of this project, we proposed a new rotation function for molecular replacement. The goal of this project is to develop a complete new molecular replacement method. The main different characteristics are that it uses Patterson vectors and can calculate phases ab initio with a small peptide fragment. This is because Patterson vectors sometimes can be more sensitive. Up to now, the related software has been completed and the speed of calculation has been increased nearly 10 times. The name of the software is PVMR. PVMR assemble MR solutions from single fragment to obtain larger MR solutions with multiple fragments. These larger MR solutions can then searched in the structural database to find similar structural domains. These similar domains can then be used as the search model for MR determination in the following step. It was discovered that such a procedure was plausible. Therefore, we have in fact developed a new ab inito method for determining MR solutions, because the selection of the search model does not depend on the sequence homology of the target protein. A paper describing the method and testing results of PVMR has been published in Acta Crystallographica A, whose impact factor now is about 50, even higher than the Nature and Science magazines.

英文关键词： molecular replace method; correlation coefficient; global search; fitness value; similar structural domain