Wilkins Angela, Erdin Serkan, Lua Rhonald, Lichtarge Olivier
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Methods Mol Biol. 2012;819:29-42. doi: 10.1007/978-1-61779-465-0_3.
The evolutionary trace (ET) is the single most validated approach to identify protein functional determinants and to target mutational analysis, protein engineering and drug design to the most relevant sites of a protein. It applies to the entire proteome; its predictions come with a reliability score; and its results typically reach significance in most protein families with 20 or more sequence homologs. In order to identify functional hot spots, ET scans a multiple sequence alignment for residue variations that correlate with major evolutionary divergences. In case studies this enables the selective separation, recoding, or mimicry of functional sites and, on a large scale, this enables specific function predictions based on motifs built from select ET-identified residues. ET is therefore an accurate, scalable and efficient method to identify the molecular determinants of protein function and to direct their rational perturbation for therapeutic purposes. Public ET servers are located at: http://mammoth.bcm.tmc.edu/.
进化踪迹（ET）是用于识别蛋白质功能决定因素，并将突变分析、蛋白质工程和药物设计靶向到蛋白质最相关位点的唯一经过充分验证的方法。它适用于整个蛋白质组；其预测带有可靠性评分；在大多数具有20个或更多序列同源物的蛋白质家族中，其结果通常具有显著性。为了识别功能热点，ET会扫描多序列比对，寻找与主要进化分歧相关的残基变异。在案例研究中，这能够实现功能位点的选择性分离、重新编码或模拟，并且在大规模情况下，这能够基于由选定的ET识别残基构建的基序进行特定功能预测。因此，ET是一种准确、可扩展且高效的方法，用于识别蛋白质功能的分子决定因素，并为治疗目的对其进行合理扰动。公共ET服务器位于：http://mammoth.bcm.tmc.edu/
