AN EVOLUTIONARY APPROACH TO FOLDING SMALL ALPHA-HELICAL PROTEINS THAT USES SEQUENCE INFORMATION AND AN EMPIRICAL GUIDING FITNESS FUNCTION
AN EVOLUTIONARY APPROACH TO FOLDING SMALL ALPHA-HELICAL PROTEINS THAT USES SEQUENCE INFORMATION AND AN EMPIRICAL GUIDING FITNESS FUNCTION
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DOI：
10.1073/pnas.91.10.4436
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发表时间：
1994-05-10
影响因子：
11.1
通讯作者：
EISENBERG, D
中科院分区：
文献类型：
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作者：
BOWIE, JU;EISENBERG, D
三个短的蛋白质序列已经被计算机引导到与它们的晶体结构相似的折叠。最初，从已知蛋白质结构的数据库中选择大小从9到25个残基的多肽片段构象。根据三维图谱分数判断，如果片段与要折叠的序列的片段相容，则选择该片段。通过将选择的片段构象连接在一起，产生了数百个与要折叠的蛋白质具有相同长度和序列的试验结构。这些起始试验结构随后通过进化算法进行了改进。用于改进结构的选择压力由能量函数提供，该能量函数被设计为引导构象搜索过程朝向正确的结构。我们发现，通过不到1400代的400个结构的进化，一些小的螺旋蛋白质的总折叠可以从序列中计算出来，对于Cα原子，与观察到的结构的偏差为2.5-4.0埃。
Three short protein sequences have been guided by computer to folds resembling their crystal structures. Initially, peptide fragment conformations ranging in size from 9 to 25 residues were selected from a database of known protein structures. A fragment was selected if it was compatible with a segment of the sequence to be folded, as judged by three-dimensional profile scores. By linking the selected fragment conformations together, hundreds of trial structures were generated of the same length and sequence as the protein to be folded. These starting trial structures were then improved by an evolutionary algorithm. Selection pressure for improving the structures was provided by an energy function that was designed to guide the conformational search procedure toward the correct structure. We find that by evolution of only 400 structures for fewer than 1400 generations, the overall fold of some small helical proteins can be computed from the sequence, with deviations from observed structures of 2.5-4.0 Angstrom for C alpha atoms.