Secció de Física Estadística i Interdisciplinària-Departament de Física de la Matèria Condensada, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
Onena Medicines S.L., Paseo Miramón 170, planta 3, B06, 20014, Donostia, Gipuzkoa, Spain.
J Phys Chem B. 2023 Jun 29;127(25):5541-5552. doi: 10.1021/acs.jpcb.3c00937. Epub 2023 Jun 19.
Unstructured proteins can modulate cellular responses to environmental conditions by undergoing coil-globule transitions and phase separation. However, the molecular mechanisms of these phenomena still need to be fully understood. Here, we use Monte Carlo calculations of a coarse-grained model incorporating water's effects on the system's free energy. Following previous studies, we modeled an unstructured protein as a polymer chain. Because we are interested in investigating how it responds to thermodynamic changes near a hydrophobic surface under different conditions, we chose an entirely hydrophobic sequence to maximize the interaction with the interface. We show that a slit pore confinement without top-down symmetry enhances the unfolding and adsorption of the chain in both random coil and globular states. Moreover, we demonstrate that the hydration water modulates this behavior depending on the thermodynamic parameters. Our findings provide insights into how homopolymers and possibly unstructured proteins can sense and adjust to external stimuli such as nanointerfaces or stresses.
无规蛋白可以通过进行螺旋-球蛋白转变和相分离来调节细胞对环境条件的响应。然而，这些现象的分子机制仍需要充分理解。在这里，我们使用包含水对系统自由能影响的粗粒化模型的蒙特卡罗计算。遵循先前的研究，我们将无规蛋白建模为聚合物链。因为我们有兴趣研究在不同条件下它如何响应疏水表面附近的热力学变化，我们选择了完全疏水的序列来最大化与界面的相互作用。我们表明，没有上下对称的狭缝孔限制增强了链在无规卷曲和球状状态下的展开和吸附。此外，我们证明水合作用可以根据热力学参数来调节这种行为。我们的发现提供了关于均聚物和可能的无规蛋白如何感知和适应外部刺激（如纳米界面或压力）的见解。
