Enhancements to ProFit

该项目将对申请人先前编写的用于比较蛋白质或RNA坐标集的计算机软件ProFit进行许多改进。这些增强功能在很大程度上是当前用户所要求的，并将使更多的应用和研究成为可能。两组或多组蛋白质或RNA坐标的最佳“拟合”是检查结构相似性和可变性的基本要求。这种拟合在基于其他已知结构预测蛋白质的三维结构和评估建模方法的性能时完成。它也被用于研究蛋白质和RNA结构的可变性和灵活性。当单个分子具有柔韧性时，当人们希望检查突变或不同结合配体对蛋白质结构的影响时，这是有用的。拟合也用于检查相关蛋白质结构的变异性，以研究蛋白质结构的进化。ProFit是一个非常广泛使用的程序，用于拟合两个或多个蛋白质或RNA结构。必须指定结构中的一组等效原子，但是ProFit也允许自动优化等效原子。一旦结构被拟合，一个被称为“均方根偏差”（RMSd）的简单统计数据被计算出来，以给出相似性的指示。本项目提出的工作将为该计划提供许多增强功能。最重要的是，将实现用户要求的一些附加功能，其中包括在处理具有多个多肽链的结构时消除限制。这一点变得尤为重要，因为晶体学家现在能够解决极其复杂的结构。我们还将对代码进行一些内部清理，使其更易于维护，并将提供Windows版本和基于web的图形界面，以提高生物学家软件的可用性。

This project will make a number of enhancements to the computer software known as ProFit previously written by the applicant for comparing sets of protein or RNA coordinates. These enhancements are largely requested by current users and will enable additional applications and research. The optimal 'fitting' of two or more sets of protein or RNA coordinates is a fundamental requirement for examining structural similarity and variability. This fitting is done when predicting the three-dimensional structure of proteins based on other known structures and in evaluating the performance of modelling methods. It is also used in studying the variability and flexibility of protein and RNA structures. This is useful when a single molecule is flexible and when one wishes to examine the effects of mutations or different bound ligands on protein structure. Fitting is also used to examine the variability of related protein structures to study evolution or protein structures. ProFit is a very widely used program for fitting two or more protein or RNA structures. A set of equivalent atoms in the structures must be specified, but ProFit also allows the equivalent atoms to be optimized automatically. Once the structures have been fitted, a simple statistic known as the 'root mean square deviation' (RMSd) is calculated to give an indication of the similarity. The work proposed in this project will provide a number of enhancements to the program. Most importantly, a number of additions requested by users will be implemented which include removing restrictions when dealing with structures having more than one poly-peptide chain. This is becoming particularly important as crystallographers are now able to solve enormously complex structures. We will also perform some internal cleanup of the code to make it more maintainable and will provide a Windows version and a web-based graphical interface to improve the usability of the software for Biologists.