Bryant S H
Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA.
Proteins. 1996 Oct;26(2):172-85. doi: 10.1002/(SICI)1097-0134(199610)26:2<172::AID-PROT7>3.0.CO;2-I.
Threading experiments with proteins from the globin family provide an indication of the nature of the structural similarity required for successful fold recognition and accurate sequence-structure alignment. Threading scores are found to rise above the noise of false positives whenever roughly 60% of residues from a sequence can be aligned with analogous sites in the structure of a remote homolog. Fold recognition specificity thus appears to be limited by the extent of structural similarity, regardless of the degree of sequence similarity. Threading alignment accuracy is found to depend more critically on the degree of structural similarity. Alignments are accurate, placing the majority of residues exactly as in structural alignment, only when superposition residuals are less than 2.5 A. These criteria for successful recognition and sequence-structure alignment appear to be consistent with the successes and failures of threading methods in blind structure prediction. They also suggest a direct assay for improved threading methods: Potentials and alignment models should be tested for their ability to detect less extensive structural similarities, and to produce accurate alignments when superposition residuals for this conserved "core" fall in the range characteristic of remote homologs.
对珠蛋白家族蛋白质进行的穿线实验表明了成功进行折叠识别和准确序列-结构比对所需的结构相似性的本质。每当序列中约60%的残基能够与远缘同源物结构中的类似位点比对时，穿线得分就会高于假阳性的噪声水平。因此，折叠识别特异性似乎受到结构相似程度的限制，而与序列相似程度无关。发现穿线比对准确性更关键地取决于结构相似程度。只有当叠加残差小于2.5埃时，比对才是准确的，能将大多数残基精确地放置在结构比对中的位置。这些成功识别和序列-结构比对的标准似乎与穿线方法在盲法结构预测中的成败一致。它们还为改进穿线方法提供了一种直接的检测方法：应测试势函数和比对模型检测不太广泛的结构相似性的能力，以及当这种保守“核心”的叠加残差落在远缘同源物特征范围内时产生准确比对的能力。
