Computing protein stabilities from their chain lengths
Computing protein stabilities from their chain lengths
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DOI：
10.1073/pnas.0903995106
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发表时间：
2009-06-30
影响因子：
11.1
通讯作者：
Dill, Ken A.
中科院分区：
文献类型：
--
作者：
Ghosh, Kingshuk;Dill, Ken A.
由于现代基因组学的发展，新的蛋白质氨基酸序列正在被快速学习。这些蛋白质的天然结构和功能通常可以用生物信息学方法推断出来。我们在这里表明，仅给出简单的基因组学信息：链长度和带电侧链的数量，也可以推断蛋白质的稳定性和热折叠特性。特别是，我们的模型预测了H(T)、S(T)、C-p和F(T)——折叠焓、熵、热容和自由能——作为温度T的函数；胍和尿素中的变性剂m值；ph -温度-盐相图，以及半径为s的腔内蛋白质的约束能量F(s)。这些相平衡的所有组合也可以从这些信息中计算出来。作为一个例子，我们计算了使一个小密闭腔内的蛋白质变性的pH值和盐条件。由于该模型是分析性的，因此它的计算效率足够高，可以用于用蛋白质稳定性信息自动注释整个蛋白质组。
New amino acid sequences of proteins are being learned at a rapid rate, thanks to modern genomics. The native structures and functions of those proteins can often be inferred using bioinformatics methods. We show here that it is also possible to infer the stabilities and thermal folding properties of proteins, given only simple genomics information: the chain length and the numbers of charged side chains. In particular, our model predicts Delta H(T), Delta S(T), Delta C-p, and Delta F(T)-the folding enthalpy, entropy, heat capacity, and free energy-as functions of temperature T; the denaturant m values in guanidine and urea; the pH-temperature-salt phase diagrams, and the energy of confinement F(s) of the protein inside a cavity of radius s. All combinations of these phase equilibria can also then be computed from that information. As one illustration, we compute the pH and salt conditions that would denature a protein inside a small confined cavity. Because the model is analytical, it is computationally efficient enough that it could be used to automatically annotate whole proteomes with protein stability information.