Mandal Manoj, Mukhopadhyay Chaitali
Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata - 700 009, India.
Phys Chem Chem Phys. 2014 Oct 21;16(39):21706-16. doi: 10.1039/c4cp01657b. Epub 2014 Sep 8.
An all atom molecular dynamics simulation was used to explore the atomic detail mechanism of guanidinium induced unfolding of the protein ubiquitin. Ubiquitin unfolds through pre-unfolded (intermediate) states, i.e. guanidinium induced unfolding of ubiquitin appears to be a multi-step process, and loss of hydrophobic contacts of C-terminal residues is crucial for ubiquitin unfolding. Free-energy landscapes show that barrier separation between folded and unfolded basins is ∼5.0 kcal mol(-1), and both the basins are of comparable energy. It was observed that guanidinium ions interact directly with ubiquitin. Favorable electrostatic interaction is the main driving force for such accumulation of guanidinium ions near protein, but van der Waals energy also contributes. RDF plots show that accumulation of guanidinium ions near specific residues is the main cause for destabilization of intra-residue interactions crucial to maintain the three-dimensional fold of the protein. One salt-bridge interaction between Lys11 and Glu34 appears to be important to maintain the crystal structure of ubiquitin and this salt-bridge can map the unfolding process of ubiquitin.
采用全原子分子动力学模拟来探究胍盐诱导蛋白质泛素展开的原子细节机制。泛素通过预展开（中间）状态展开，即胍盐诱导的泛素展开似乎是一个多步过程，并且C末端残基疏水接触的丧失对泛素展开至关重要。自由能景观表明折叠态和未折叠态盆地之间的势垒分离约为5.0千卡/摩尔（-1），并且两个盆地具有相当的能量。观察到胍盐离子直接与泛素相互作用。有利的静电相互作用是胍盐离子在蛋白质附近如此积累的主要驱动力，但范德华能也有贡献。径向分布函数图表明，胍盐离子在特定残基附近的积累是对维持蛋白质三维折叠至关重要的残基内相互作用不稳定的主要原因。赖氨酸11和谷氨酸34之间的一个盐桥相互作用似乎对维持泛素的晶体结构很重要，并且这个盐桥可以描绘泛素的展开过程。
