The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PP II) structure. While intrinsic PP II propensities have been measured for the common biological amino acids in short peptides, the ability of these experimentally determined propensities to quantitatively reproduce structural behavior in intrinsically disordered proteins (IDPs) has not been established. Presented here are results from molecular simulations of disordered proteins showing that the hydrodynamic radius (R h) can be predicted from experimental PP II propensities with good agreement, even when charge-based considerations are omitted. The simulations demonstrate that R h and chain propensity for PP II structure are linked via a simple power-law scaling relationship, which was tested using the experimental R h of 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. Charge effects on R h were found to be generally weak when compared to PPII effects on Rh. Results from this study indicate that the hydrodynamic dimensions of IDPs are evidence of considerable sequence-dependent backbone propensities for PPII structure that qualitatively, if not quantitatively, match conformational propensities measured in peptides.
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机译:人们认为无序蛋白的特性取决于聚脯氨酸II(PP II)结构的固有构象倾向。虽然已测量了短肽中常见生物氨基酸的内在PP II倾向,但尚未建立这些实验确定的倾向来定量再现内在无序蛋白(IDP)中结构行为的能力。这里展示的是无序蛋白质分子模拟的结果,表明即使不考虑基于电荷的考虑,也可以从实验PP II倾向中很好地预测流体动力学半径(R h)。仿真表明,PP II结构的R h和链倾向性通过简单的幂律比例关系进行链接,该关系使用22个IDP的实验R h进行了测试,涵盖了广泛的肽长度,净电荷和序列组成。与 PP em> II em>对 R em> h em>的影响相比,对R h的电荷影响通常较弱。这项研究的结果表明,IDPs的水动力尺度是 PP em> II em>结构相当大的序列依赖性骨架倾向的证据,即使不是定量的,其也可以定性地与在肽。
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