Functionally important positions can comprise the majority of a protein's architecture.
Functionally important positions can comprise the majority of a protein's architecture.
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功能上重要的位置可以构成蛋白质结构的大部分。
DOI：
10.1002/prot.22985
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Swint-Kruse,Liskin
中科院分区：
文献类型：
--
作者：
Tungtur,Sudheer;Parente,DanielJ;Swint-Kruse,Liskin
伴随着基因组时代的到来，许多生物信息学程序已经被开发出来，用于从蛋白质家族的序列比对中识别功能重要的位置。为了评估这些分析，许多人使用了LacI/GalR家族，并确定预测为“重要”的位置是否通过已发表的实验验证。然而，我们以前注意到，预测并不能确定所有的实验上重要的位置存在于这些同源物的连接区。为了调和这些差异，我们修正并扩展了常用于序列/功能分析的LacI/GalR序列集。接下来，对（1）整个LacI/GalR序列集和（2）在其接头中具有功能重要的“YxPxxxAxxL”基序的同源物子集进行了各种分析。设计这种策略是为了确定是否可以通过基于知识的序列排序来改进预测，并且对于某些分析，确实增加了识别的接头位置的数量。然而，两个功能上重要的接头位置没有通过任何分析可靠地鉴定。最后，我们将新的预测与所有已知的实验数据进行了比较。coliLacI和三个同源接头。由此，我们估计>50%的位置对LacI/GalR同源物的功能是重要的。在推论中，中性位置可能不太频繁地出现，并且可能在序列分析中更容易检测。尽管分析已经成功地引导了部分交换蛋白质功能的突变，但对蛋白质家族中序列/功能关系的更好的实验理解将有助于揭示自然界用于进化新蛋白质功能的剩余规则。Proteins 2011; © 2011 Wiley利斯，Inc.
Concomitant with the genomic era, many bioinformatics programs have been developed to identify functionally important positions from sequence alignments of protein families. To evaluate these analyses, many have used the LacI/GalR family and determined whether positions predicted to be “important” are validated by published experiments. However, we previously noted that predictions do not identify all of the experimentally important positions present in the linker regions of these homologs. In an attempt to reconcile these differences, we corrected and expanded the LacI/GalR sequence set commonly used in sequence/function analyses. Next, a variety of analyses were carried out (1) for the entire LacI/GalR sequence set and (2) for a subset of homologs with functionally‐important “YxPxxxAxxL” motifs in their linkers. This strategy was devised to determine whether predictions could be improved by knowledge‐based sequence sorting and—for some analyses—did increase the number of linker positions identified. However, two functionally important linker positions were not reliably identified by any analysis. Finally, we compared the new predictions to all known experimental data forE. coli LacI and three homologous linkers. From these, we estimate that >50% of positions are important to the functions of the LacI/GalR homologs. In corollary, neutral positions might occur less frequently and might be easier to detect in sequence analyses. Although analyses have successfully guided mutations that partially exchange protein functions, a better experimental understanding of the sequence/function relationships in protein families would be helpful for uncovering the remaining rules used by nature to evolve new protein functions. Proteins 2011; © 2011 Wiley‐Liss, Inc.
DOI：
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发表时间：
1994
期刊：
影响因子：
--
作者：
R. Conaway;J. Conaway
通讯作者：
J. Conaway