Natively unfolded protein stability as a coil-to-globule transition in charge/hydropathy space
Natively unfolded protein stability as a coil-to-globule transition in charge/hydropathy space
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DOI：
10.1021/ja802124e
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发表时间：
2008-07-23
影响因子：
15
通讯作者：
Hatch, Harold W.
中科院分区：
文献类型：
--
作者：
Ashbaugh, Henry S.;Hatch, Harold W.
在没有实验分配的情况下，用于预测天然未折叠蛋白质序列的经验电荷/亲水相关性（Uversky, V. N.；Gillespie, J. R.；Fink, A. L. Proteins: Struct., Funct., Genet. 2060, 41, 415-427）可能提供了总多肽构象的最直观描述。这种相关性的成功取决于基本链长度独立于扩展构象和紧凑构象之间的边界线，相反，分别通过高电荷/弱疏水残基或弱电荷/高疏水残基来稳定。我们展示了粗粒度多肽在各种序列疏水性、电荷和长度上的广泛模拟结果。观察到序列组成空间中的线圈到球体的转变，类似于电荷/水病相关性。仅当明确包含带电肽的抗衡离子时，才会发现接近序列长度独立的稳定性边界，这是球表面排斥静电相互作用的抗衡离子凝聚稳定的结果。观察到的抗衡离子吸附与理论凝结预测在数量上一致。我们认为，除了电荷和疏水性之外，根据经验已知与构象紊乱相关的替代功能可以纳入我们的极简多肽模型中，以研究未折叠序列的独立预测因子之间的相互作用。
In the absence of experimental assignments, the empirical charge/hydropathy correlation for the prediction of natively unfolded protein sequences (Uversky, V. N.; Gillespie, J. R.; Fink, A. L. Proteins: Struct., Funct., Genet. 2060, 41, 415-427) provides perhaps the most intuitive description of gross polypeptide conformation. The success of this correlation rests on an essential chain length independence of the boundary line between expanded and compact conformations, conversely stabilized by highly charged/weakly hydrophobic residues or weakly charged/highly hydrophobic residues, respectively. We present extensive simulation results for coarse-grained polypeptides over a wide range of sequence hydrophobicities, charges, and lengths. A coil-to-globule transition in sequence composition space analogous to the charge/ hydropathy correlation is observed. A near sequence length independent stability boundary is only found when counterions for the charged peptides are explicitly included, as a result of counterion condensation stabilization of repulsive electrostatic interactions on the globule surface. The observed counterion adsorption is shown to be in quantitative agreement with theoretical condensation predictions. We argue that alternate functionalities, beyond charge and hydrophobicity, empirically known to correlate with conformational disorder can be incorporated into our minimalist polypeptide model to study the interplay between independent predictors of unfolded sequences.