Smith W Wendell, Ho Po-Yi, O'Hern Corey S
Department of Physics, Yale University, New Haven, Connecticut 06520-8120, USA and Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520-8114, USA.
Department of Physics, Yale University, New Haven, Connecticut 06520-8120, USA.
Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Oct;90(4):042709. doi: 10.1103/PhysRevE.90.042709. Epub 2014 Oct 13.
We perform extensive coarse-grained (CG) Langevin dynamics simulations of intrinsically disordered proteins (IDPs), which possess fluctuating conformational statistics between that for excluded volume random walks and collapsed globules. Our CG model includes repulsive steric, attractive hydrophobic, and electrostatic interactions between residues and is calibrated to a large collection of single-molecule fluorescence resonance energy transfer data on the interresidue separations for 36 pairs of residues in five IDPs: α-, β-, and γ-synuclein, the microtubule-associated protein τ, and prothymosin α. We find that our CG model is able to recapitulate the average interresidue separations regardless of the choice of the hydrophobicity scale, which shows that our calibrated model can robustly capture the conformational dynamics of IDPs. We then employ our model to study the scaling of the radius of gyration with chemical distance in 11 known IDPs. We identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.
我们对内在无序蛋白(IDP)进行了广泛的粗粒度(CG)朗之万动力学模拟,这类蛋白在排除体积随机游走和塌缩球状体之间具有波动的构象统计特征。我们的CG模型包括残基间的排斥性空间位阻、吸引性疏水作用和静电相互作用,并根据五个IDP(α-、β-和γ-突触核蛋白、微管相关蛋白τ和前胸腺素α)中36对残基间间距的大量单分子荧光共振能量转移数据进行了校准。我们发现,无论疏水性标度如何选择,我们的CG模型都能够重现平均残基间间距,这表明我们校准后的模型能够稳健地捕捉IDP的构象动力学。然后,我们使用我们的模型研究了11种已知IDP中回转半径与化学距离的标度关系。我们确定了在平均电荷和疏水性空间中,与折叠蛋白和IDP之间分界线的距离与沿蛋白质的回转半径随化学距离的标度指数之间存在很强的相关性。