Flexibility and mobility in mesophilic and thermophilic homologous proteins from molecular dynamics and FoldUnfold method.
Flexibility and mobility in mesophilic and thermophilic homologous proteins from molecular dynamics and FoldUnfold method.
复制标题
通过分子动力学和 FoldUnfold 方法研究嗜温和嗜热同源蛋白的灵活性和移动性。
DOI：
10.1142/s0219720010004690
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发表时间：
2010
影响因子：
1
通讯作者：
Galzitskaya,OxanaV
中科院分区：
文献类型：
--
作者：
Mamonova,TatyanaB;Glyakina,AnnaV;Kurnikova,MariaG;Galzitskaya,OxanaV
蛋白质分子的刚性和柔性是其正常功能的基础，因此快速准确地预测蛋白质的刚性和柔性是蛋白质科学中的重要问题之一。在这项工作中，我们使用了两种理论方法来确定灵活的区域在四个同源对蛋白质的嗜热和嗜温生物。在这项研究中选择的蛋白质对被选为代表四个典型的折叠类。我们的第一种方法，FoldUnfold，使用已知球状蛋白三级结构中氨基酸接触密度的氨基酸序列和统计信息。这种基于知识的方法的主要优点是它的计算速度和在缺乏蛋白质的三维（3D）结构的情况下进行预测的能力。第二种方法使用基于图论的刚性簇分解称为第一，与分子动力学（MD）模拟已知结构的蛋白质一起应用。虽然MD模拟很耗时，但它们是研究蛋白质物理性质的最直接方法，包括它们的刚性/柔性。用这两种方法预测的柔性区域吻合较好。我们还表明，一个网站的高流动性并不一定表明其高灵活性，反之亦然。在我们的模拟中，嗜热蛋白质比它们的嗜温同源物更不灵活。在所有种类的嗜温蛋白质中发现了更长的柔性环。
To function properly protein molecules require both flexibility and rigidity, therefore fast and accurate prediction of protein rigidity/flexibility is one of the important problems in protein science. In this work we used two theoretical approaches to determine flexible regions in four homologous pairs of proteins from thermophilic and mesophilic organisms. Protein pairs chosen in this study were selected to represent four typical folding classes. Our first approach, FoldUnfold, uses amino acid sequence and statistical information on the density of contacts of amino acids in tertiary structures of known globular proteins. The main advantages of such knowledge-based methodology are its computational speed and ability to make predictions in the absence of three-dimensional (3D) structure of a protein. The second approach uses a graph theory-based rigid cluster decomposition termed FIRST, applied together with Molecular Dynamics (MD) simulations of proteins with known structure. While MD simulations are time-consuming, they are the most direct way of studying physical properties of proteins, including their rigidity/flexibility. Flexible regions predicted by both methods in this work were in good agreement with each other. We also showed that high mobility of a site is not necessarily indicative of its high flexibility and vice versa. In our simulations thermophile proteins were less flexible than their mesophilic homologues. Longer flexible loops were found in mesophilic proteins of all classes.