ANALYSIS AND PREDICTION OF THE PACKING OF ALPHA-HELICES AGAINST A BETA-SHEET IN THE TERTIARY STRUCTURE OF GLOBULAR-PROTEINS
ANALYSIS AND PREDICTION OF THE PACKING OF ALPHA-HELICES AGAINST A BETA-SHEET IN THE TERTIARY STRUCTURE OF GLOBULAR-PROTEINS
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DOI：
10.1016/0022-2836(82)90144-9
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发表时间：
1982-01-01
影响因子：
5.6
通讯作者：
TAYLOR, WR
中科院分区：
文献类型：
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作者：
COHEN, FE;STERNBERG, MJE;TAYLOR, WR
α的包装螺旋和β-纸张为6 α/。β的分析蛋白质（例如黄素氧还蛋白）。结果为预测α的三级结构的计算机算法提供了基础。β的蛋白质从其氨基酸序列和实际分配的二级结构。个人的包装α-螺旋对β-一般包括2个相邻的。α-上有4行非极性残基在位置i、i + 4、i + 8、i + 1、i + 5、i + 9处的螺旋。相互作用的模式片材残留物是由片材表面的扭曲性质和伴随的侧链旋转产生的。在更详细的水平上，4个α-螺旋残基（i + 1，i + 4，i + 5和i + 8）形成围绕一个特定β-片状残基，通常为异亮氨酸、亮氨酸或缬氨酸。通常，α-螺旋位于10埃。在片材上方并且平行于股线方向。预测遵循组合方法。首先，列出可能的β-通过生成所有的β-半导体来构造片状结构（106至1014），片拓扑和β-链比对。该列表通过拓扑结构和非极性残基的位置的限制来减少，以介导片材/螺旋包装，然后根据氢键的程度进行排序。该算法被均匀地应用于16 α/。β的13个蛋白质的结构域。对于每个结构，简化列表中的1个成员接近晶体结构;原子平均为5.6埃。对于100个残基。对于α/。β的具有纯平行β-的蛋白质片，结构的总数相当于或优于天然的H-键是1和148之间。对于具有混合β-最坏的情况是甘油醛-3-磷酸脱氢酶，其中必须对多达3800个结构进行采样。这些结果的进化意义以及潜在的使用组合的方法来蛋白质折叠问题进行了讨论。
The packing of .alpha.-helices and .beta.-sheets in 6 .alpha./.beta. proteins (e.g. flavodoxin) was analyzed. The results provide the basis for a computer algorithm to predict the tertiary structure of an .alpha..beta. protein from its amino acid sequence and actual assignment of secondary structure. The packing of an individual .alpha.-helix against a .beta.-sheet generally involves 2 adjacent .+-. 4 rows of non-polar residues on the .alpha.-helix at the positions i, i + 4, i + 8, i + 1, i + 5, i + 9. The pattern of interacting .beta.-sheet residues results from the twisted nature of the sheet surface and the attendant rotation of the side-chains. At a more detailed level,4 of the .alpha.-helical residues (i + 1, i + 4, i + 5 and i + 8) form a diamond that surrounds one particular .beta.-sheet residue, generally isoleucine, leucine or valine. In general, the .alpha.-helix sits 10 .ANG. above the sheet and lies parallel to the strand direction. The prediction follows a combinational approach. First, a list of possible .beta.-sheet structures (106 to 1014) is constructed by the generation of all .beta.-sheet topologies and .beta.-strand alignments. This list is reduced by constraints on topology and the location of non-polar residues to mediate the sheet/helix packing, and then rank-ordered on the extent of H-bonding. This algorithm was uniformly applied to 16 .alpha./.beta. domains in 13 proteins. For every structure, 1 member of the reduced list was close to the crystal structure; the root-mean-square deviation between equivalenced C.alpha. atoms averaged 5.6 .ANG. for 100 residues. For the .alpha./.beta. proteins with pure parallel .beta.-sheets, the total number of structures comparable to or better than the native in terms of H-bonds was between 1 and 148. For proteins with mixed .beta.-sheets, the worst case is glyceraldehyde-3-phosphate dehydrogenase, where as many as 3800 structures would have to be sampled. The evolutionary significance of these results as well as the potential use of a combinatorial approach to the protein folding problem are discussed.