Baruah Anupaul, Biswas Parbati
Department of Chemistry, University of Delhi, Delhi, India.
Phys Chem Chem Phys. 2016 Aug 17;18(33):23207-14. doi: 10.1039/c6cp03185d.
The charge-hydrophobicity correlation of globular and disordered proteins is explored using a generalized self-consistent field theoretical method combined with Monte Carlo simulations. Globular and disordered protein sequences with varied mean net charge and mean hydrophobicity are designed by theory, while Metropolis Monte Carlo generates a suitable ensemble of conformations. Results imply a transition of the dominant interactions between globular and disordered proteins across the charge-hydrophobicity boundary. It is observed that the charge-hydrophobicity boundary actually represents a trade-off between the repulsive and attractive interactions in a protein sequence. The attractive interactions predominate on the globular side of the boundary, while the repulsive interactions prevail on the disordered side. For globular proteins, core forming hydrophobic interactions are dominant leading to a minimally frustrated native conformation. For disordered proteins, the repulsive electrostatic interactions prevail yielding a minimally frustrated region comprising of an expanded, dynamic conformational ensemble. Thus, protein disorder, like protein folding, satisfies the principle of minimal frustration. All results are compared to real globular and disordered proteins. Thus this algorithm may be useful to probe the conformational characteristics of disordered proteins.
利用广义自洽场理论方法结合蒙特卡罗模拟，探索了球状蛋白和无序蛋白的电荷-疏水性相关性。通过理论设计了具有不同平均净电荷和平均疏水性的球状和无序蛋白序列，而 metropolis 蒙特卡罗方法生成了合适的构象集合。结果表明，球状蛋白和无序蛋白之间的主导相互作用在电荷-疏水性边界处发生转变。据观察，电荷-疏水性边界实际上代表了蛋白质序列中排斥和吸引相互作用之间的权衡。在边界的球状一侧，吸引相互作用占主导，而在无序一侧，排斥相互作用占主导。对于球状蛋白，形成核心的疏水相互作用占主导，导致天然构象的受挫程度最小。对于无序蛋白，排斥性静电相互作用占主导，产生一个由扩展的、动态构象集合组成的受挫程度最小的区域。因此，蛋白质无序与蛋白质折叠一样，满足最小受挫原则。所有结果都与真实的球状和无序蛋白进行了比较。因此，该算法可能有助于探究无序蛋白的构象特征。
