Li H, Helling R, Tang C, Wingreen N
NEC Research Institute, 4 Independence Way, Princeton, NJ 08540, USA.
Science. 1996 Aug 2;273(5275):666-9. doi: 10.1126/science.273.5275.666.
Protein structures in nature often exhibit a high degree of regularity (for example, secondary structure and tertiary symmetries) that is absent from random compact conformations. With the use of a simple lattice model of protein folding, it was demonstrated that structural regularities are related to high "designability" and evolutionary stability. The designability of each compact structure is measured by the number of sequences that can design the structure-that is, sequences that possess the structure as their nondegenerate ground state. Compact structures differ markedly in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess "proteinlike" secondary structure and even tertiary symmetries. In addition, they are thermodynamically more stable than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.
自然界中的蛋白质结构通常呈现出高度的规则性（例如二级结构和三级对称性），而随机紧密构象则没有这种规则性。通过使用一种简单的蛋白质折叠晶格模型，研究表明结构规则性与高“可设计性”和进化稳定性相关。每个紧密结构的可设计性通过能够设计该结构的序列数量来衡量，即具有该结构作为其非简并基态的序列。紧密结构在可设计性方面有显著差异；高度可设计的结构出现时，与之相关的序列数量远高于平均水平。这些高度可设计的结构具有“类蛋白质”的二级结构甚至三级对称性。此外，它们在热力学上比其他结构更稳定。这些结果表明，自然界中选择蛋白质结构是因为它们易于设计且对突变具有稳定性，并且这种选择同时导致了热力学稳定性。
