Using protein homology models for structure-based studies: Approaches to model refinement
Using protein homology models for structure-based studies: Approaches to model refinement
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DOI：
10.1100/tsw.2006.250
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Fernandes, M. X.
中科院分区：
文献类型：
--
作者：
Kairys, V.;Gilson, M. K.;Fernandes, M. X.
同源性建模是一种计算方法，用于在实验数据不可用时将目标蛋白质分配到3-D结构。该方法使用另一种具有已知结构的蛋白质作为模板，该蛋白质与靶标具有一定的序列同一性。最粗糙的方法是将目标蛋白质骨架原子穿在模板蛋白质的骨架原子上，但需要必要的细化方法来产生逼真的模型。在这个微型审查锚定范围内的药物设计，我们显示了使用蛋白质的同源模型在发现潜在的治疗靶点的粘合剂的有效性。我们还报告了几种不同的方法来同源模型的细化，从非常简单到最详细的。结果表明，细化方法是系统依赖性的，更精细的方法并不总是与更好的性能从建立同源模型。
Homology modeling is a computational methodology to assign a 3-D structure to a target protein when experimental data are not available. The methodology uses another protein with a known structure that shares some sequence identity with the target as a template. The crudest approach is to thread the target protein backbone atoms over the backbone atoms of the template protein, but necessary refinement methods are needed to produce realistic models. In this mini-review anchored within the scope of drug design, we show the validity of using homology models of proteins in the discovery of binders for potential therapeutic targets. We also report several different approaches to homology model refinement, going from very simple to the most elaborate. Results show that refinement approaches are system dependent and that more elaborate methodologies do not always correlate with better performances from built homology models.