Hierarchical and multi-resolution representation of protein flexibility
Hierarchical and multi-resolution representation of protein flexibility
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DOI：
10.1093/bioinformatics/btl481
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发表时间：
2006-11-15
期刊：
影响因子：
5.8
通讯作者：
Sanner, Michel
中科院分区：
文献类型：
--
作者：
Zhao, Yong;Stoffler, Daniel;Sanner, Michel
动机：在广泛的生物系统中观察到分子相互作用过程中的构象重排。然而，以模拟和预测分子相互作用为目的的计算方法仍然在很大程度上忽略了生物大分子的柔性性质，因为使用蛮力表示时自由度数在计算上是困难的。结果：在本文中，我们提出了一种称为柔性树(FT)的计算数据结构，该结构实现了分子柔性的多分辨率和层次化编码。这种树状数据结构允许对蛋白质构象空间的相对较小但复杂的子空间进行编码。这些构象的子空间由少量的变量来参数化，并且可以使用标准的全局搜索技术进行有效的搜索。FT结构使其可以直接组合和嵌套各种运动类型，如铰链、剪切、扭转、螺杆、旋转式侧链、正常模式和基本动力学。此外，将形状分配给FT中的节点的能力允许对灵活的蛋白质形状进行交互操作，并以交互方式可视化构象变化对蛋白质整体形状的影响。我们描述了FT的设计，并说明了这种树的构建，以分层地组合从各种来源获得的运动信息，从实验到用户直觉，并描述不同生物尺度上的构象变化。我们表明，各种类型的运动的组合有助于细化编码的构象子空间，以包括实验确定的结构，并且我们演示了在这些子空间中搜索特定的构象。联系：Sanner@scripps.edu.补充信息：补充数据可在BioInformation Online上获得。
Motivation: Conformational rearrangements during molecular interactions are observed in a wide range of biological systems. However, computational methods that aim at simulating and predicting molecular interactions are still largely ignoring the flexible nature of biological macromolecules as the number of degrees of freedom is computationally intractable when using brute force representations.Results: In this article, we present a computational data structure called the Flexibility Tree (FT) that enables a multi-resolution and hierarchical encoding of molecular flexibility. This tree-like data structure allows the encoding of relatively small, yet complex sub-spaces of a protein's conformational space. These conformational sub-spaces are parameterized by a small number of variables and can be searched efficiently using standard global search techniques. The FT structure makes it straightforward to combine and nest a wide variety of motion types such as hinge, shear, twist, screw, rotameric side chains, normal modes and essential dynamics. Moreover, the ability to assign shapes to the nodes in a FT allows the interactive manipulation of flexible protein shapes and the interactive visualization of the impact of conformational changes on the protein's overall shape. We describe the design of the FT and illustrate the construction of such trees to hierarchically combine motion information obtained from a variety of sources ranging from experiment to user intuition, and describing conformational changes at different biological scales. We show that the combination of various types of motion helps refine the encoded conformational sub-spaces to include experimentally determined structures, and we demonstrate searching these sub-spaces for specific conformations.Contact: sanner@scripps.eduSupplementary information: Supplementary Data are available at Bioinformatics online.