Wakana H, Yokomizo H, Wako H, Isogai Y, Kosuge K, Saito N
Int J Pept Protein Res. 1984 Jun;23(6):657-70. doi: 10.1111/j.1399-3011.1984.tb03139.x.
The unfolding pathway of lysozyme was investigated by carrying out the computer simulation. Taking into account the simultaneous change of both the dihedral angels phi and psi of a residue, we explore the detailed features of the conformational energy profiles. The triangle distance map shows that the lysozyme molecule is divided into three domains, 1-40, 41-101 and 102-129 in amino acid residue numbers (referred to as the domains I, II and III, respectively). The calculated unfolding process indicates that in the early stage of unfolding domain III located at the C-terminal begins to be detached from the other two, and then domain I can be unfolded. The long-range interactions between domains I and III stabilize the whole molecule and give the cooperative nature of the folding. The calculated unfolding pathway of lysozyme is consistent with the folding pathway proposed by Anderson & Wetlaufer [J. Biol. Chem. (1976). 251, 3147-3153] who identified the disulfide bondings in the early stage of the glutathione regeneration. A simplified treatment of unfolding for myoglobin is also discussed in the Appendix.
通过计算机模拟研究了溶菌酶的去折叠途径。考虑到残基的二面角φ和ψ的同时变化，我们探索了构象能量分布的详细特征。三角形距离图显示，溶菌酶分子在氨基酸残基数量上分为三个结构域，即1 - 40、41 - 101和102 - 129（分别称为结构域I、II和III）。计算得到的去折叠过程表明，在去折叠的早期，位于C端的结构域III开始与其他两个结构域分离，然后结构域I可以去折叠。结构域I和III之间的长程相互作用稳定了整个分子，并赋予了折叠的协同性质。计算得到的溶菌酶去折叠途径与Anderson和Wetlaufer [《生物化学杂志》（1976年）。251, 3147 - 3153]提出的折叠途径一致，他们在谷胱甘肽再生的早期阶段鉴定了二硫键。附录中还讨论了对肌红蛋白去折叠的简化处理。
