Williams M A, Thornton J M, Goodfellow J M
Department of Crystallography, Birkbeck College, London, UK.
Protein Eng. 1997 Aug;10(8):895-903. doi: 10.1093/protein/10.8.895.
A novel modelling procedure, which rapidly unfolds a protein by enhancing solvent penetration of its core, was used to investigate the unfolding pathway of hen egg-white lysozyme. Early on the unfolding pathway there is a dramatic disruption of the tertiary contacts within the protein, which decouples its domains. Subsequently, the helical domain slowly loses its compactness and the helices fluctuate rapidly. The protein then adopts a 'molten globule-like' structure in which the native beta-sheet is essentially intact. The modelled structures have properties similar to those of lysozyme's experimentally characterized partially folded states and provide insight into its complex (un)folding process. The sequence of unfolding events shows how the unfolding pathway of a multidomain protein may be most similar to its fastest, but not necessarily its dominant, folding pathway.
一种通过增强溶剂对蛋白质核心的渗透来快速展开蛋白质的新型建模程序，被用于研究鸡蛋清溶菌酶的展开途径。在展开途径的早期，蛋白质内部的三级接触发生了剧烈破坏，使其结构域解耦。随后，螺旋结构域逐渐失去其紧密性，螺旋快速波动。该蛋白质随后采用了一种“类熔球”结构，其中天然β-折叠基本保持完整。所模拟的结构具有与溶菌酶实验表征的部分折叠状态相似的性质，并为其复杂的（去）折叠过程提供了见解。展开事件的顺序表明了多结构域蛋白质的展开途径如何可能与其最快但不一定是最主要的折叠途径最为相似。
