BACKGROUND The details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold symmetric scaffold, despite the proteins' low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular β-trefoil proteins by constructing an average distance map (ADM) and utilizing inter-residue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values. We compare our sequence-based prediction results with the packing between hydrophobic residues in native 3D structures and a Gō-model simulation. RESULTS The ADM and F-value analyses predict that the N-terminal and C-terminal regions are compact and that the hydrophobic residues at the central region can be regarded as an interaction center with other residues. These results correspond well to those of the Gō-model simulations. Moreover, our results indicate that the irregular parts in the β-trefoil proteins do not hinder the protein formation. Conserved hydrophobic residues on the β5 strand are always the interaction center of packing between the conserved hydrophobic residues in both regular and irregular β-trefoil proteins. CONCLUSIONS We revealed that the β5 strand plays an important role in β-trefoil protein structure construction. The sequence-based methods used in this study can extract the protein folding information from only amino acid sequence data, and well corresponded to 3D structure-based Gō-model simulation and available experimental results.

中文翻译：

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通过基于序列的技术和Gō模型模拟分析不规则β-三叶折叠蛋白的折叠位点。

背景技术对于许多蛋白质，折叠机制的细节尚未完全理解，并且据信关于蛋白质的折叠机制的信息是在其氨基酸序列中编码的。已知β-三叶蛋白具有相同的3D支架，即三重对称支架，尽管该蛋白在超家族之间的序列同一性较低。在这项研究中，我们通过构建平均距离图（ADM）并利用残基间平均距离统计数据确定残基对的相对接触频率，从不规则β-三叶蛋白的氨基酸序列中提取了一个初始折叠单元。 F值。我们将基于序列的预测结果与本机3D结构中疏水残基之间的填充和Gō模型模拟进行比较。结果ADM和F值分析预测N末端和C末端区域是致密的，中心区域的疏水残基可被视为与其他残基的相互作用中心。这些结果与Gō模型模拟的结果非常吻合。此外，我们的结果表明，β-三叶形蛋白质中的不规则部分不会阻碍蛋白质的形成。β5链上保守的疏水残基始终是规则和不规则β-三叶蛋白中保守的疏水残基之间堆积的相互作用中心。结论我们揭示了β5链在β-三叶蛋白的结构构建中起着重要作用。本研究中使用的基于序列的方法只能从氨基酸序列数据中提取蛋白质折叠信息，