College of Chemistry and Molecular Engineering, and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing, China.
School of Economics and Management, Tsinghua University, Beijing, China.
Protein Sci. 2022 Jul;31(7):e4375. doi: 10.1002/pro.4375.
In statistical mechanics, it is well known that the huge number of degrees of freedom does not complicate the problem as it seems, but actually greatly simplifies the analysis (e.g., to give a Boltzmann distribution). Here, we reveal that the ensemble averaging from the vast conformations of intrinsically disordered proteins (IDPs) greatly simplifies the nature of binding affinity, which can be reliably decomposed into a sum of the ligandability of IDP and the capacity of ligand. Such an unexpected regularity is applied to facilitate the virtual screening upon IDPs. It also provides essential insight in understanding the specificity difference between IDPs and conventional ordered proteins since the specificity is caused by deviation from the baseline behavior of protein-ligand binding.
在统计力学中，人们熟知的是，大量的自由度并没有像看起来那样使问题复杂化，实际上却大大简化了分析（例如，给出玻尔兹曼分布）。在这里，我们揭示了从本质上无序的蛋白质（IDPs）的大量构象中进行的系综平均，极大地简化了结合亲和力的本质，而结合亲和力可以可靠地分解为 IDP 的配体能力和配体的容量之和。这种出乎意料的规律性可用于促进 IDP 的虚拟筛选。由于特异性是由偏离蛋白质-配体结合的基线行为引起的，因此它还为理解 IDP 和传统有序蛋白质之间的特异性差异提供了重要的见解。
