Integrated Graduate Program in Physical & Engineering Biology, Yale University, New Haven, Connecticut.
Department of Chemistry, Yale University, New Haven, Connecticut.
Proteins. 2020 Sep;88(9):1154-1161. doi: 10.1002/prot.25884. Epub 2020 Mar 5.
There have been several studies suggesting that protein structures solved by NMR spectroscopy and X-ray crystallography show significant differences. To understand the origin of these differences, we assembled a database of high-quality protein structures solved by both methods. We also find significant differences between NMR and crystal structures-in the root-mean-square deviations of the C atomic positions, identities of core amino acids, backbone, and side-chain dihedral angles, and packing fraction of core residues. In contrast to prior studies, we identify the physical basis for these differences by modeling protein cores as jammed packings of amino acid-shaped particles. We find that we can tune the jammed packing fraction by varying the degree of thermalization used to generate the packings. For an athermal protocol, we find that the average jammed packing fraction is identical to that observed in the cores of protein structures solved by X-ray crystallography. In contrast, highly thermalized packing-generation protocols yield jammed packing fractions that are even higher than those observed in NMR structures. These results indicate that thermalized systems can pack more densely than athermal systems, which suggests a physical basis for the structural differences between protein structures solved by NMR and X-ray crystallography.
已经有几项研究表明，通过 NMR 光谱和 X 射线晶体学解析的蛋白质结构存在显著差异。为了了解这些差异的起源，我们组装了一个由这两种方法解析的高质量蛋白质结构的数据库。我们还发现 NMR 和晶体结构之间存在显著差异——在 C 原子位置的均方根偏差、核心氨基酸的同一性、骨架和侧链二面角以及核心残基的堆积分数。与之前的研究不同，我们通过将蛋白质核心建模为氨基酸形状粒子的堆积来确定这些差异的物理基础。我们发现，我们可以通过改变用于生成堆积的热化程度来调整堆积的堆积分数。对于非热化方案，我们发现平均堆积分数与通过 X 射线晶体学解析的蛋白质结构核心中观察到的堆积分数相同。相比之下，高度热化的堆积生成方案产生的堆积分数甚至高于在 NMR 结构中观察到的堆积分数。这些结果表明，热化系统可以比非热化系统更紧密地堆积，这为通过 NMR 和 X 射线晶体学解析的蛋白质结构之间的结构差异提供了物理基础。
