Hagler A T, Honig B
Proc Natl Acad Sci U S A. 1978 Feb;75(2):554-8. doi: 10.1073/pnas.75.2.554.
In this paper we carry out computer simulation studies of some of the factors responsible for protein tertiary structure. We show that it is possible to obtain (fold) a compact globular conformation from a sequence of amino acids consisting of only glycines and alanines. Our results indicate that glycines play a central role in stabilizing globular structures by facilitating the formation of turns and by destabilizing helical structures. Using this simple two-amino-acid representation, which serves as a control experiment, we are able to obtain a conformation that resembles the native structure of pancreatic trypsin inhibitor, as closely as any obtained previously in folding studies. However, careful examination reveals that the true chain topology has not been reproduced here or in previous studies. We suggest that the discrepancies between calculated and observed structures are more significant than the similarities. The implications of these results for the validity of models for protein folding, the use of pancreatic trypsin inhibitor in folding studies, and the possible role of glycine in the evolution of protein structure are discussed.
在本文中，我们对一些决定蛋白质三级结构的因素进行了计算机模拟研究。我们表明，从仅由甘氨酸和丙氨酸组成的氨基酸序列中有可能获得（折叠成）紧密的球状构象。我们的结果表明，甘氨酸通过促进转角的形成和破坏螺旋结构的稳定性，在稳定球状结构中起着核心作用。使用这种简单的双氨基酸表示法作为对照实验，我们能够获得一种与胰蛋白酶抑制剂天然结构相似的构象，其相似程度与此前折叠研究中获得的任何构象一样。然而，仔细检查发现，这里以及之前的研究都没有重现真正的链拓扑结构。我们认为，计算结构与观察结构之间的差异比相似性更为显著。本文还讨论了这些结果对蛋白质折叠模型有效性、折叠研究中胰蛋白酶抑制剂的使用以及甘氨酸在蛋白质结构进化中可能作用的影响。
