Laboratory of Computational and Quantitative Biology, LCQB, UMR 7238 CNRS, IBPS, Sorbonne Université, Paris, France.
Toulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
Methods Mol Biol. 2023;2627:83-100. doi: 10.1007/978-1-0716-2974-1_5.
Homology modeling is the most common technique to build structural models of a target protein based on the structure of proteins with high-sequence identity and available high-resolution structures. This technique is based on the idea that protein structure shows fewer changes than sequence through evolution. While in this scenario single mutations would minimally perturb the structure, experimental evidence shows otherwise: proteins with high conformational diversity impose a limit of the paradigm of comparative modeling as the same protein sequence can adopt dissimilar three-dimensional structures. These cases present challenges for modeling; at first glance, they may seem to be easy cases, but they have a complexity that is not evident at the sequence level. In this chapter, we address the following questions: Why should we care about conformational diversity? How to consider conformational diversity when doing template-based modeling in a practical way?
同源建模是根据高序列同一性和具有高分辨率结构的蛋白质结构来构建目标蛋白质结构模型的最常用技术。该技术基于蛋白质结构在进化过程中比序列变化小的观点。虽然在这种情况下，单个突变对结构的影响最小，但实验证据表明并非如此：具有高构象多样性的蛋白质对比较建模的范例施加了限制，因为相同的蛋白质序列可以采用不同的三维结构。这些情况对建模提出了挑战；乍一看，它们似乎是简单的情况，但它们具有在序列水平上不明显的复杂性。在本章中，我们将解决以下问题：为什么我们应该关心构象多样性？在实际进行基于模板的建模时，如何考虑构象多样性？
