Verma Deeptak, Guo Jun-Tao, Jacobs Donald J, Livesay Dennis R
Department of Bioinformatics and Genomics, University of North Carolina, Charlotte, NC, USA.
Methods Mol Biol. 2014;1084:239-54. doi: 10.1007/978-1-62703-658-0_13.
The Distance Constraint Model (DCM) is a computational modeling scheme that uniquely integrates thermodynamic and mechanical descriptions of protein structure. As such, quantitative stability-flexibility relationships (QSFR) that describe the interrelationships of thermodynamics and mechanics can be quickly computed. Using comparative QSFR analyses, we have previously investigated these relationships across a small number of protein orthologs, ranging from two to a dozen [1, 2]. However, our ultimate goal is provide a comprehensive analysis of whole protein families, which requires consideration of many more structures. To that end, we have developed homology modeling and assessment protocols so that we can robustly calculate QSFR properties for proteins without experimentally derived structures. The approach, which is presented here, starts from a large ensemble of potential homology models and uses a clustering algorithm to identify the best models, thus paving the way for a comprehensive QSFR analysis across hundreds of proteins in a protein family.
距离约束模型（DCM）是一种计算建模方案，它独特地整合了蛋白质结构的热力学和力学描述。因此，可以快速计算出描述热力学和力学相互关系的定量稳定性-灵活性关系（QSFR）。通过比较QSFR分析，我们之前已经研究了少数蛋白质直系同源物之间的这些关系，数量从两个到十二个不等[1,2]。然而，我们的最终目标是对整个蛋白质家族进行全面分析，这需要考虑更多的结构。为此，我们开发了同源建模和评估协议，以便能够在没有实验获得的结构的情况下稳健地计算蛋白质的QSFR特性。本文介绍的方法从大量潜在的同源模型开始，使用聚类算法识别最佳模型，从而为对蛋白质家族中数百种蛋白质进行全面的QSFR分析铺平道路。
