Zhai Yanqin, Martys Nicos S, George William L, Curtis Joseph E, Nayem Jannatun, Z Y, Liu Yun
Materials and Construction Research Division of Engineering Laboratory, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899, USA.
Information Technology Laboratory, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899, USA.
Struct Dyn. 2021 Apr 8;8(2):024102. doi: 10.1063/4.0000086. eCollection 2021 Mar.
In the past decade, there was increased research interest in studying internal motions of flexible proteins in solution using Neutron Spin Echo (NSE) as NSE can simultaneously probe the dynamics at the length and time scales comparable to protein domain motions. However, the collective intermediate scattering function (ISF) measured by NSE has the contributions from translational, rotational, and internal motions, which are rather complicated to be separated. Widely used NSE theories to interpret experimental data usually assume that the translational and rotational motions of a rigid particle are decoupled and independent to each other. To evaluate the accuracy of this approximation for monoclonal antibody (mAb) proteins in solution, dissipative particle dynamic computer simulation is used here to simulate a rigid-body mAb for up to about 200 ns. The total ISF together with the ISFs due to only the translational and rotational motions as well as their corresponding effective diffusion coefficients is calculated. The aforementioned approximation introduces appreciable errors to the calculated effective diffusion coefficients and the ISFs. For the effective diffusion coefficient, the error introduced by this approximation can be as large as about 10% even though the overall agreement is considered reasonable. Thus, we need to be cautious when interpreting the data with a small signal change. In addition, the accuracy of the calculated ISFs due to the finite computer simulation time is also discussed.
在过去十年中，使用中子自旋回波（NSE）研究溶液中柔性蛋白质的内部运动引起了越来越多的研究兴趣，因为NSE能够同时在与蛋白质结构域运动相当的长度和时间尺度上探测动力学。然而，通过NSE测量的集体中间散射函数（ISF）包含平移、旋转和内部运动的贡献，这些贡献很难分离。广泛用于解释实验数据的NSE理论通常假设刚性粒子的平移和旋转运动是解耦的且相互独立。为了评估这种近似对于溶液中单克隆抗体（mAb）蛋白质的准确性，本文使用耗散粒子动力学计算机模拟来模拟一个刚体mAb长达约200纳秒。计算了总ISF以及仅由平移和旋转运动引起的ISF及其相应的有效扩散系数。上述近似对计算出的有效扩散系数和ISF引入了明显的误差。对于有效扩散系数，即使总体一致性被认为是合理的，这种近似引入的误差也可能高达约10%。因此，在解释信号变化较小的数据时我们需要谨慎。此外，还讨论了由于有限的计算机模拟时间导致的计算ISF的准确性。
