Water Distribution and Clustering on the Lyophilized IgG1 Surface: Insight from Molecular Dynamics Simulations.,Molecular Pharmaceutics

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Water Distribution and Clustering on the Lyophilized IgG1 Surface: Insight from Molecular Dynamics Simulations.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-01-28 , DOI: 10.1021/acs.molpharmaceut.9b01150
Shaoxin Feng ₁ , Günther H J Peters ₂ , Satoshi Ohtake ₃ , Christian Schöneich ₄ , Evgenyi Shalaev ₁

Affiliation

Water has a critical role in the stability of the higher-order structure of proteins. In addition, it is considered to be a major destabilization factor for the physical and chemical stability of freeze-dried proteins and peptides. Physical and chemical aspects of protein/water relationships are commonly studied with the use of water vapor sorption isotherms for amorphous lyophilized proteins, which, in turn, are commonly analyzed using the Brunauer-Emmett-Teller (BET) equation to obtain the parameters, Wm and CB. The parameter Wm is generally referred to as the "monolayer limit of adsorption" and has a narrow range of 6-8% for most proteins. In this study, the water distribution on an IgG1 surface is investigated by molecular dynamics (MD) simulations at different water contents. The monolayer of water molecules was found to have limited coverage of the protein surface, and the true monolayer coverage of the protein globule actually occurs at a hydration level above 30%. The distribution of water molecules on the IgG1 surface is also highly heterogeneous, and the heterogeneity is not considered in the BET theory. In this study, a mechanistic model has been developed to describe the water vapor sorption isotherm. This model is based on the analysis of the hydrogen bonding network extracted from the MD simulations. The model is consistent with the experimental Type-II isotherm, which is usually observed for proteins. The physical meaning of the BET monolayer was redefined as the onset of water cluster formation. A simple model to calculate the onset water level, Wm, is proposed based on the hydration of different amino acids, as determined from the MD simulations.

中文翻译：

冻干的IgG1表面上的水分布和聚集：分子动力学模拟的见解。

水在蛋白质高级结构的稳定性中起着关键作用。另外，它被认为是冻干蛋白质和肽的物理和化学稳定性的主要不稳定因素。通常使用无定形冻干蛋白质的水蒸气吸附等温线研究蛋白质/水关系的物理和化学方面，然后通常使用Brunauer-Emmett-Teller（BET）方程进行分析以获得参数Wm和CB。参数Wm通常被称为“吸附的单层极限”，并且对于大多数蛋白质而言具有6-8％的狭窄范围。在这项研究中，通过分子动力学（MD）模拟研究了不同水分含量下IgG1表面的水分布。发现水分子的单层对蛋白质表面的覆盖有限，而蛋白质小球的真正单层覆盖实际上发生在水合度高于30％的情况下。IgG1表面上水分子的分布也是高度异质的，并且在BET理论中未考虑异质性。在这项研究中，已开发出一种机械模型来描述水蒸气吸附等温线。该模型基于从MD模拟中提取的氢键网络的分析。该模型与通常观察到蛋白质的II型等温线实验相符。BET单层的物理含义被重新定义为水簇形成的开始。一个简单的模型来计算起始水位Wm

更新日期：2020-02-12

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