EXPLORING CONFORMATIONAL SPACE WITH A SIMPLE LATTICE MODEL FOR PROTEIN-STRUCTURE
EXPLORING CONFORMATIONAL SPACE WITH A SIMPLE LATTICE MODEL FOR PROTEIN-STRUCTURE
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DOI：
10.1016/0022-2836(94)90040-x
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发表时间：
1994-11-04
影响因子：
5.6
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
HINDS, DA;LEVITT, M
我们提出了一个低分辨率晶格模型，我们可以为小蛋白质详尽地生成所有可能的紧凑主链构象。使用简单的结构和能量标准，对于各种蛋白质，我们可以选择与其已知的天然结构具有显着相似性的晶格结构。我们的能量参数基于实验确定的结构数据库中的成对氨基酸接触频率。我们方法中的一个关键步骤涉及将序列线程化到每个晶格模型上，从而形成三级相互作用的局部最优模式。我们根据覆盖所有构象空间的结构收集的统计数据以及排列序列收集的统计数据来评估我们的结果。尽管模型分辨率较低，但我们的低能结构包含许多固有特征。这些结果表明。序列疏水性的总体模式显着限制了序列可能采用的折叠范围。
We present a low resolution lattice model for which we can exhaustively generate all possible compact backbone conformations for small proteins. Using simple structural and energetic criteria, for a variety of proteins, we can select for lattice structures that have significant similarities with their known native structures. Our energetic parameters are based on pairwise amino acid contact frequencies in a database of experimentally determined structures. A key step in our method involves the threading of a sequence onto every lattice model, such that a locally optimal pattern of tertiary interactions is formed. We evaluate our results against statistics collected for structures covering all of conformational space, and against statistics collected for permuted sequences. Despite the low resolution of the model, our low energy structures contain many native features. These results indicate that. the overall pattern of hydrophobicity of a sequence significantly constrains the range of folds that sequence is likely to adopt.