Hinds D A, Levitt M
Beckman Laboratories for Structural Biology, Department of Structural Biology, Stanford University School of Medicine, CA 94305.
J Mol Biol. 1994 Nov 4;243(4):668-82. doi: 10.1016/0022-2836(94)90040-x.
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.
我们提出了一种低分辨率晶格模型，利用该模型我们可以详尽地生成小蛋白质所有可能的紧密主链构象。通过简单的结构和能量标准，对于多种蛋白质，我们可以选择出与其已知天然结构具有显著相似性的晶格结构。我们的能量参数基于实验测定结构数据库中氨基酸对的接触频率。我们方法中的一个关键步骤是将序列穿到每个晶格模型上，从而形成局部最优的三级相互作用模式。我们根据为覆盖所有构象空间的结构收集的统计数据以及为置换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，但我们的低能量结构包含许多天然特征。这些结果表明，序列疏水性的整体模式显著限制了该序列可能采用的折叠范围。
