Hinge Atlas: relating protein sequence to sites of structural flexibility.
Hinge Atlas: relating protein sequence to sites of structural flexibility.
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DOI：
10.1186/1471-2105-8-167
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发表时间：
2007-05-22
影响因子：
3
通讯作者：
Gerstein MB
中科院分区：
文献类型：
--
作者：
Flores SC;Lu LJ;Yang J;Carriero N;Gerstein MB
将蛋白质序列的特征与结构铰链联系起来对于识别结构域边界、理解结构功能关系以及设计蛋白质的灵活性具有重要意义。由于缺乏适当的数据集来研究铰链的特性，这一领域的努力受到了阻碍。利用分子运动数据库，我们创建了手动注释铰链的铰链图谱和用于计算这些铰链中各种类型残基富集的统计形式。我们发现铰链与序列特征之间存在各种相关性。其中一些是预料之中的；例如，我们发现铰链往往出现在表面和线圈和旋转中，并且富含小的亲水残留物。其他的则不那么明显和直观。特别是，我们发现铰链倾向于与活性位点重合，但与后者不同的是，它们在进化中根本不保守。我们评估了基于序列的铰链预测的潜力。运动在催化和蛋白质-配体相互作用中起着重要作用。铰链弯曲运动是已知运动中最大的一类。因此，将铰链位置与残基类型、理化类别、二级结构、溶剂暴露、进化保守性以及与活性位点的接近性等序列特征联系起来是很重要的。为此，我们首先生成了Hinge Atlas，这是一组手工标注了铰链位置的蛋白质运动，然后研究了这些特征与铰链位置的重合。我们发现所有的特征都与铰链位置有关。最有趣的是，我们发现铰链往往发生在活性位点或附近，但不像后者是保守的。不那么令人惊讶的是，我们发现铰链残基往往很小，不疏水或脂肪族，并且在表面上依次出现和随机卷曲。利用本研究产生的部分数据，建立了一个基于功能序列的铰链预测器。铰链图集可供社区进一步的灵活性研究。
Relating features of protein sequences to structural hinges is important for identifying domain boundaries, understanding structure-function relationships, and designing flexibility into proteins. Efforts in this field have been hampered by the lack of a proper dataset for studying characteristics of hinges. Using the Molecular Motions Database we have created a Hinge Atlas of manually annotated hinges and a statistical formalism for calculating the enrichment of various types of residues in these hinges. We found various correlations between hinges and sequence features. Some of these are expected; for instance, we found that hinges tend to occur on the surface and in coils and turns and to be enriched with small and hydrophilic residues. Others are less obvious and intuitive. In particular, we found that hinges tend to coincide with active sites, but unlike the latter they are not at all conserved in evolution. We evaluate the potential for hinge prediction based on sequence. Motions play an important role in catalysis and protein-ligand interactions. Hinge bending motions comprise the largest class of known motions. Therefore it is important to relate the hinge location to sequence features such as residue type, physicochemical class, secondary structure, solvent exposure, evolutionary conservation, and proximity to active sites. To do this, we first generated the Hinge Atlas, a set of protein motions with the hinge locations manually annotated, and then studied the coincidence of these features with the hinge location. We found that all of the features have bearing on the hinge location. Most interestingly, we found that hinges tend to occur at or near active sites and yet unlike the latter are not conserved. Less surprisingly, we found that hinge residues tend to be small, not hydrophobic or aliphatic, and occur in turns and random coils on the surface. A functional sequence based hinge predictor was made which uses some of the data generated in this study. The Hinge Atlas is made available to the community for further flexibility studies.
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DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
影响因子：
2.9
作者：
Hayward, S;Lee, RA
通讯作者：
Lee, RA
影响因子：
5.6
作者：
Dumontier, M;Yao, R;Hogue, CWV
通讯作者：
Hogue, CWV
影响因子：
5.6
作者：
GARNIER, J;OSGUTHORPE, DJ;ROBSON, B
通讯作者：
ROBSON, B