On the role of structural information in remote homology detection and sequence alignment: New methods using hybrid sequence profiles
On the role of structural information in remote homology detection and sequence alignment: New methods using hybrid sequence profiles
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DOI：
10.1016/j.jmb.2003.10.025
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发表时间：
2003-12-12
影响因子：
5.6
通讯作者：
Honig, B
中科院分区：
文献类型：
--
作者：
Tang, CL;Xie, L;Honig, B
结构比对经常揭示蛋白质之间的关系，这些关系不能单独使用序列比对来检测。然而，还没有发现完全基于单独的结构比对的概况搜索方法在寻找远程同源物方面是有效的。在这里，我们探讨了远程同源检测和序列比对的结构信息的作用。为此，我们开发了一系列的混合多维比对配置文件，联合收割机组合的序列，二级和三级结构信息到混合配置文件。基于序列的谱是其位置特异性评分矩阵仅来源于序列比对的谱;基于结构的谱是来源于多个结构比对的谱。我们比较纯序列为基础的配置文件，纯结构为基础的配置文件，以及混合配置文件，使用组合的序列和结构为基础的配置文件，其中基于序列的配置文件中使用的环/基序区域和结构信息中使用的核心结构区域。所有的混合方法提供了显着的改进，简单的轮廓到轮廓对齐。我们表明，基于序列和基于结构的配置文件有助于远程同源性检测和比对的准确性，并且每个包含一些独特的信息。我们讨论了这些结果的影响，进一步改进氨基酸序列和结构分析。(C)2003爱思唯尔有限公司。保留所有权利。
Structural alignments often reveal relationships between proteins that cannot be detected using sequence alignment alone. However, profile search methods based entirely on structural alignments alone have not been found to be effective in finding remote homologs. Here, we explore the role of structural information in remote homolog detection and sequence alignment. To this end, we develop a series of hybrid multidimensional alignment profiles that combine sequence, secondary and tertiary structure information into hybrid profiles. Sequence-based profiles are profiles whose position-specific scoring matrix is derived from sequence alignment alone; structure-based profiles are those derived from multiple structure alignments. We compare pure sequence-based profiles to pure structure-based profiles, as well as to hybrid profiles that use combined sequence-and-structure-based profiles, where sequence-based profiles are used in loop/motif regions and structural information is used in core structural regions. All of the hybrid methods offer significant improvement over simple profile-to-profile alignment. We demonstrate that both sequence-based and structure-based profiles contribute to remote homology detection and alignment accuracy, and that each contains some unique information. We discuss the implications of these results for further improvements in amino acid sequence and structural analysis. (C) 2003 Elsevier Ltd. All rights reserved.