Peto Myron, Kloczkowski Andrzej, Jernigan Robert L
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011-3020.
J Phys Condens Matter. 2007 Jul 18;19(28):285220-285230. doi: 10.1088/0953-8984/19/28/285220.
One important problem in computational structural biology is protein designability, that is, why protein sequences are not random strings of amino acids but instead show regular patterns that encode protein structures. Many previous studies that have attempted to solve the problem have relied upon reduced models of proteins. In particular, the 2D square and the 3D cubic lattices together with reduced amino acid alphabet models have been examined extensively and have lead to interesting results that shed some light on evolutionary relationship among proteins. Here we perform designability studies on the 2D square lattice and explore the effects of variable overall shapes on protein designability using a binary hydrophobic-polar (HP) amino acid alphabet. Because we rely on a simple energy function that counts the total number of H-H interactions between non-sequential residues, we restrict our studies to protein shapes that have the same number of residues and also a constant number of non-bonded contacts. We have found that there is a marked difference in the designability between various protein shapes, with some of them accounting for a significantly larger share of the total foldable sequences.
计算结构生物学中的一个重要问题是蛋白质可设计性，即为什么蛋白质序列不是氨基酸的随机串，而是呈现出编码蛋白质结构的规则模式。许多先前试图解决该问题的研究都依赖于蛋白质的简化模型。特别是，二维正方形和三维立方体晶格以及简化氨基酸字母模型已经得到了广泛研究，并得出了一些有趣的结果，这些结果揭示了蛋白质之间的进化关系。在这里，我们对二维正方形晶格进行可设计性研究，并使用二元疏水-极性（HP）氨基酸字母表探索可变整体形状对蛋白质可设计性的影响。由于我们依赖于一个简单的能量函数，该函数计算非连续残基之间H-H相互作用的总数，因此我们将研究限制在具有相同残基数且非键合接触数恒定的蛋白质形状上。我们发现，各种蛋白质形状之间的可设计性存在显著差异，其中一些形状在可折叠序列总数中所占份额明显更大。
