Department of Chemistry, Indian Institute of Technology, Guwahati, Assam, 781039, India.
Department of Chemistry, Indian Institute of Technology, Guwahati, Assam, 781039, India.
Arch Biochem Biophys. 2020 Nov 30;695:108484. doi: 10.1016/j.abb.2020.108484. Epub 2020 Jul 28.
The event of protein folding is associated with essential biological functionalities and unfolding of protein native state can cause intra-cellular toxicity leading to biological dysfunctions and even cell death. The present study discusses the folding-unfolding equilibrium of the small globular protein Trp-cage in presence of denaturing and protecting osmolytes urea and choline-O-sulfate (COS), respectively, employing Replica Exchange Molecular Dynamics (REMD), extensive free energy calculations and temperature scanned free energy landscapes. It is shown that, while 6 M urea quite easily denatures the protein, 0.5 M and 1 M COS is able to protect the protein from urea induced denaturation at room temperature. However, REMD simulations reveal that while the protein in pure water can withstand a simulation temperature as high as 420 K without melting, the protecting effect of 0.5 M and 1 M COS is operative up to 300 and 340 K respectively. This study furnishes evidences to shed light into the protecting mechanism of COS regarding urea induced protein unfolding, thereby putting forward the use of COS as a proper protecting osmolyte towards different types of proteins.
蛋白质折叠的事件与基本的生物功能有关，蛋白质天然状态的展开会导致细胞内毒性，从而导致生物功能障碍甚至细胞死亡。本研究讨论了在变性和保护渗透剂脲和胆碱-O-硫酸盐（COS）存在下，小分子球状蛋白 Trp-cage 的折叠-展开平衡，分别采用复制交换分子动力学（REMD）、广泛的自由能计算和温度扫描自由能景观。结果表明，虽然 6 M 脲很容易使蛋白质变性，但 0.5 M 和 1 M COS 能够在室温下保护蛋白质免受脲诱导的变性。然而，REMD 模拟表明，虽然纯水中的蛋白质可以在不熔化的情况下承受高达 420 K 的模拟温度，但 0.5 M 和 1 M COS 的保护作用分别在 300 和 340 K 时有效。这项研究提供了证据，阐明了 COS 针对脲诱导的蛋白质展开的保护机制，从而提出将 COS 用作针对不同类型蛋白质的合适保护渗透剂。
