Muppirala Usha K, Li Zhijun
Bioinformatics Program, University of the Sciences in Philadelphia Philadelphia, PA 19104, USA.
Protein Eng Des Sel. 2006 Jun;19(6):265-75. doi: 10.1093/protein/gzl009. Epub 2006 Mar 24.
Evolutionarily conserved hydrophobic residues at the core of protein structures are generally assumed to play a structural role in protein folding and stability. Recent studies have implicated that their importance to protein structures is uneven, with a few of them being crucial and the rest of them being secondary. In this work, we explored the possibility of employing this feature of native structures for discriminating non-native structures from native ones. First, we developed a network tool to quantitatively measure the structural contributions of individual amino acid residues. We systematically applied this method to diverse fold-type sets of native proteins. It was confirmed that this method could grasp the essential structural features of native proteins. Next, we applied it to a number of decoy sets of proteins. The results indicate that such an approach indeed identified non-native structures in most test cases. This finding should be of help for the investigation of the fundamental problem of protein structure prediction.
一般认为，蛋白质结构核心处进化上保守的疏水残基在蛋白质折叠和稳定性方面发挥着结构作用。最近的研究表明，它们对蛋白质结构的重要性并不均匀，其中少数残基至关重要，其余的则是次要的。在这项工作中，我们探索了利用天然结构的这一特征来区分非天然结构和天然结构的可能性。首先，我们开发了一种网络工具来定量测量单个氨基酸残基的结构贡献。我们系统地将此方法应用于各种折叠类型的天然蛋白质组。证实了该方法能够掌握天然蛋白质的基本结构特征。接下来，我们将其应用于许多蛋白质的诱饵组。结果表明，这种方法确实在大多数测试案例中识别出了非天然结构。这一发现应该有助于蛋白质结构预测这一基本问题的研究。
