Desjarlais J R, Handel T M
University of Calfornia at Berkeley, USA.
Curr Opin Biotechnol. 1995 Aug;6(4):460-6. doi: 10.1016/0958-1669(95)80076-x.
Initially, it was hoped that very simple rules could be sued to design proteins that embody all the characteristics of natural proteins. Indeed, with single-domain proteins as targets, it has been possible to design proteins that adopt the desired global fold. Yet, designed proteins with well defined structures and properties that mimic those of natural proteins remain elusive. Recent efforts in protein design have been directed toward addressing the basis for non-native characteristics in most protein designs. Although it is clear that specific tertiary interactions between all residues in a protein contribute to the final folded state, much attention has been placed on optimizing the packing of side chains in the hydrophobic core, with substantial success.
最初，人们希望可以使用非常简单的规则来设计体现天然蛋白质所有特征的蛋白质。的确，以单结构域蛋白质为目标，已经有可能设计出具有所需整体折叠的蛋白质。然而，具有明确结构和性质且能模仿天然蛋白质的设计蛋白质仍然难以实现。蛋白质设计领域最近的努力旨在解决大多数蛋白质设计中出现非天然特征的原因。虽然很明显蛋白质中所有残基之间的特定三级相互作用有助于最终的折叠状态，但人们已将大量注意力放在优化疏水核心中侧链的堆积上，并取得了显著成功。
