School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
J Phys Chem B. 2009 Dec 10;113(49):16059-64. doi: 10.1021/jp907999e.
Quantum mechanical computations of proteins based on the molecular fragment approach have been carried out, and polarized protein-specific charges have been derived to provide accurate electrostatic interactions for a benchmark set of proteins. Our study shows that, under the polarized protein-specific force field, the native structure indeed corresponds to the lowest-energy conformation for these proteins. In contrast, when a standard mean-field force field such as AMBER is used, the energies of many decoy structures of proteins could be lower than those of the native structures. Furthermore, MD simulations were carried out and verified that the native structures of these proteins not only are statically more stable but are also dynamically more stable under the polarized protein-specific force field. The present results, together with several recent studies, provide strong evidence that protein polarization is critical to stabilizing the native structures of proteins.
基于分子片段方法的蛋白质量子力学计算已经完成，并推导出极化的蛋白质特异性电荷，以提供基准蛋白质组的准确静电相互作用。我们的研究表明，在极化的蛋白质特异性力场下，天然结构确实对应于这些蛋白质的最低能量构象。相比之下，当使用标准的平均场力场（如 AMBER）时，许多蛋白质的诱饵结构的能量可能低于天然结构的能量。此外，进行了 MD 模拟并验证了在极化的蛋白质特异性力场下，这些蛋白质的天然结构不仅在静态上更稳定，而且在动力学上也更稳定。这些结果与最近的几项研究一起，为蛋白质极化对稳定蛋白质天然结构的重要性提供了有力证据。
