Tomasso Maria E, Tarver Micheal J, Devarajan Deepa, Whitten Steven T
Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas, United States of America.
PLoS Comput Biol. 2016 Jan 4;12(1):e1004686. doi: 10.1371/journal.pcbi.1004686. eCollection 2016 Jan.
The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PPII) structure. While intrinsic PPII 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 (Rh) can be predicted from experimental PPII propensities with good agreement, even when charge-based considerations are omitted. The simulations demonstrate that Rh and chain propensity for PPII structure are linked via a simple power-law scaling relationship, which was tested using the experimental Rh of 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. Charge effects on Rh 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.
无序蛋白质的特性被认为取决于多聚脯氨酸II（PPII）结构的内在构象倾向。虽然已经测量了短肽中常见生物氨基酸的内在PPII倾向，但这些通过实验确定的倾向能否定量再现内在无序蛋白质（IDP）的结构行为尚未得到证实。本文展示了无序蛋白质分子模拟的结果，结果表明，即使忽略基于电荷的因素，流体力学半径（Rh）也可以根据实验得到的PPII倾向进行预测，且吻合度良好。模拟结果表明，Rh与PPII结构的链倾向通过一个简单的幂律缩放关系相联系，该关系通过22种IDP的实验Rh进行了验证，这些IDP涵盖了广泛的肽长度、净电荷和序列组成。与PPII对Rh的影响相比，电荷对Rh的影响通常较弱。这项研究的结果表明，IDP的流体力学尺寸证明了PPII结构存在相当大的序列依赖性主链倾向，这些倾向在定性上（即使不是定量上）与肽中测量的构象倾向相匹配。
