Shakhnovich E I, Gutin A M
Institute of Protein Research, Academy of Sciences of the USSR, Moscow Region.
Nature. 1990 Aug 23;346(6286):773-5. doi: 10.1038/346773a0.
Natural proteins exhibit essentially two-state thermodynamics, with one stable fold that dominates thermodynamically over a vast number of possible folds, a number that increases exponentially with the size of the protein. Here we address the question of whether this feature of proteins is a rare property selected by evolution or whether it is in fact true of a significant proportion of all possible protein sequences. Using statistical procedures developed to study spin glasses, we show that, given certain assumptions, the probability that a randomly synthesized protein chain will have a dominant fold (which is the global minimum of free energy) is a function of temperature, and that below a critical temperature the probability rapidly increases as the temperature decreases. Our results suggest that a significant proportion of all possible protein sequences could have a thermodynamically dominant fold.
天然蛋白质本质上呈现出两态热力学特性，具有一种稳定的折叠结构，在大量可能的折叠结构中，这种结构在热力学上占主导地位，而可能的折叠结构数量会随着蛋白质大小呈指数级增长。在此，我们探讨蛋白质的这一特性是进化所选择的罕见属性，还是实际上所有可能的蛋白质序列中有很大一部分都具备这一特性。通过运用为研究自旋玻璃而开发的统计程序，我们表明，在某些假设条件下，随机合成的蛋白质链具有主导折叠结构（即自由能的全局最小值）的概率是温度的函数，并且在低于临界温度时，该概率会随着温度降低而迅速增加。我们的研究结果表明，所有可能的蛋白质序列中有很大一部分可能具有热力学上的主导折叠结构。
