Predicting allosteric communication in myosin via a conserved residue pathway

This project contains the AlloPathFinder application that allows users to compute likely allosteric pathways in proteins. The underlying assumption is that residues participating in allosteric communication should be fairly conserved and that communication happens through residues that are close in space. The initial application for the code provided was to study the allosteric communication in myosin. Myosin is a well-studied molecular motor protein that walks along actin filaments to achieve cellular tasks such as movement of cargo proteins.It couples ATP hydrolysis to highly-coordinated conformational changes that result in a power-stroke motion, or ''walking'' of myosin. Communication between a set of residues must link the three functional regions of myosin and transduce energy: the catalytic ATP binding region, the lever arm, and the actin-binding domain. We are investigating which residues are likely to participate in allosteric communication pathways. <br/><br/>This project includes the following software/data packages: <br/> <ul> <li> <a href="https://simtk.org/frs?group_id=167#pack_238">AlloPathFinder </a> : The application Allopathfinder facilitates the computation of the "best paths" between two locations in a protein 'structure'. Please <b> download the AlloPathFinderUsersGuide.pdf first </b> to learn about the application. For instructions on how to reproduce the paths for the structures in Figure 3 of our publication <b> please download the file RunningAlloPathFinder.txt </b> under 'Documentation Links' below. </li> <li> <a href="https://simtk.org/frs?group_id=167#pack_239">AlloPathFinderExampleData </a> : This package contains additional PDB files that can be used as examples for running the AlloPathFinder software. Consult RunningAlloPathFinder.txt in the AlloPathFinder Package on how to use these in conjunction with the MyosinMSA_158.aln multiple alignment file to reproduce the paths reported in Figure 3 of JMB 373,1361–1373. </li> </ul>

本课题集成了AlloPathFinder应用程序，该程序允许用户计算蛋白质中可能的别构途径。其基本假设是参与别构通讯的残基应具有较高的保守性，且通讯通过空间上邻近的残基进行。该代码的初始应用旨在研究肌球蛋白中的别构通讯。肌球蛋白是一种研究广泛的分子马达蛋白，它沿着肌动蛋白丝移动以完成细胞任务，如运输蛋白质。肌球蛋白将ATP水解与高度协调的构象变化耦合，从而产生动力冲程运动，即肌球蛋白的‘行走’。一组残基之间的通讯必须连接肌球蛋白的三个功能区域并转化能量：催化ATP结合区域、杠杆臂和肌动蛋白结合域。我们正在研究哪些残基可能参与别构通讯途径。

本课题包含以下软件/数据包：

<ul>
<li><a href="https://simtk.org/frs?group_id=167#pack_238">AlloPathFinder</a>：Allopathfinder应用程序有助于计算蛋白质结构中两个位置之间的“最佳路径”。请首先下载并阅读<b>AlloPathFinderUsersGuide.pdf</b>以了解该应用程序的使用方法。有关如何重现我们出版物中图3所示结构的路径的说明，请下载下方‘Documentation Links’下的<b>RunningAlloPathFinder.txt</b>文件。</li>
<li><a href="https://simtk.org/frs?group_id=167#pack_239">AlloPathFinderExampleData</a>：此包包含额外的PDB文件，可作为运行AlloPathFinder软件的示例。有关如何使用这些文件与MyosinMSA_158.aln多重比对文件结合以重现JMB 373,1361–1373中图3所示的路径的说明，请参阅AlloPathFinder包中的RunningAlloPathFinder.txt文件。</li>
</ul>