What can disulfide bonds tell us about protein energetics, function and folding: Simulations and bioninformatics analysis
What can disulfide bonds tell us about protein energetics, function and folding: Simulations and bioninformatics analysis
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DOI：
10.1006/jmbi.2000.3893
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发表时间：
2000-07-21
影响因子：
5.6
通讯作者：
Shakhnovich, EI
中科院分区：
文献类型：
--
作者：
Abkevich, VI;Shakhnovich, EI
我们研究了二硫键对蛋白质稳定性和折叠的影响。使用晶格模型模拟，我们表明，形成一个二硫键稳定蛋白质的程度取决于连接的半胱氨酸残基之间的距离沿着链。然而，二硫键对折叠动力学的影响变化很大，从二硫化物引入折叠核或接近折叠核时的加速到二硫化物引入核外时的减慢。在确定了二硫键对稳定性的影响之后，我们研究了二硫键的数量与某些氨基酸类别的组成之间的相关性，目的是将其用作有助于蛋白质稳定性的因素的统计探针。我们发现，二硫化物的数量是负相关的脂肪族疏水，但不芳香族含量。令人惊讶的是，我们观察到二硫化物含量与极性（Q，S，T，N）氨基酸含量的强相关性和与带电（E，D，K，R）含量的强负相关性。这些发现提供了对决定蛋白质稳定性的因素和蛋白质设计的原则以及二硫键和蛋白质功能的可能关系的见解。(C)北京大学出版社.
We study the impact of disulfide bonds on protein stability and folding. Using lattice model simulations, we show that formation of a disulfide bond stabilizes a protein to an extent that depends on the distance along the chain between linked cysteine residues. However, the impact of disulfide bonds on folding kinetics varies broadly, from acceleration when disulfides are introduced in or close to the folding nucleus, to slowing when disulfides are introduced outside the nucleus. Having established the effect of disulfide bonds on stability, we study the correlation between the number of disulfide bonds and the composition of certain amino acid classes with the goal to use it as a statistical probe into factors that contribute to stability of proteins. We find that the number of disulfides is negatively correlated with aliphatic hydrophobic but not aromatic content. It is surprising that we observe a strong correlation of disulfide content with polar (Q,S,T,N) amino acid content and a strong negative correlation with charged (E,D,K,R) content. These findings provide insights into factors that determine protein stability and principles of protein design as well as possible relations of disulfide bonds and protein function. (C) 2000 Academic Press.