Hirschmann Frank, Lopez Hender, Roosen-Runge Felix, Seydel Tilo, Schreiber Frank, Oettel Martin
Institute for Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
School of Physics, Clinical and Optometric Sciences, Technological University Dublin, Grangegorman D07 ADY7, Ireland.
J Chem Phys. 2023 Feb 28;158(8):084112. doi: 10.1063/5.0132493.
We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045 (2012)] and is employed here to compare findings for the compact BSA molecule and the more anisotropic IgG molecule. We define several modified coarse-grained models of BSA and IgG, which differ in their internal constraints and thus account for a variation of flexibility. We study denser solutions of the coarse-grained models with purely repulsive molecules (achievable by suitable salt conditions) and address the effect of packing and flexibility on dynamic and static behavior. Translational and rotational self-diffusivity is enhanced for more elastic models. Finally, we discuss a number of effective sphere sizes for the BSA molecule, which can be defined from its static and dynamic properties. Here, it is found that the effective sphere diameters lie between 4.9 and 6.1 nm, corresponding to a relative spread of about ±10% around a mean of 5.5 nm.
我们构建了一个基于结构的、粗粒度的、低分辨率的牛血清白蛋白（BSA，蛋白质数据银行编号：4F5S）六珠柔性模型，牛血清白蛋白是生物物理研究中球状蛋白的一个常见例子。该模型通过对单个分子进行全原子模拟并直接进行玻尔兹曼反演得到，其特定形式是从大量六珠粗粒度模型中，使用两个合适的度量标准挑选出来的，这两个度量标准用于量化稀溶液极限下全原子和粗粒度布朗动力学模拟中集体坐标分布的一致性。对于免疫球蛋白G（IgG），文献中已引入了类似的基于结构的十二珠模型[乔德里等人，《物理化学杂志B》116, 8045 (2012)]，本文采用该模型来比较紧密的BSA分子和更具各向异性的IgG分子的研究结果。我们定义了几种BSA和IgG的改进粗粒度模型，它们的内部约束不同，因此考虑了柔性的变化。我们研究了具有纯排斥分子的粗粒度模型的更浓溶液（可通过合适的盐条件实现），并探讨了堆积和柔性对动态和静态行为的影响。对于弹性更大的模型，平移和旋转自扩散系数会增强。最后，我们讨论了BSA分子的一些有效球体尺寸，这些尺寸可根据其静态和动态性质来定义。在此发现，有效球体直径在4.9至6.1纳米之间，相对于平均直径5.5纳米的相对偏差约为±10%。
