Fernández Ariel
Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Eur J Biochem. 2002 Sep;269(17):4165-8. doi: 10.1046/j.1432-1033.2002.03116.x.
A structuring and eventual exclusion of water surrounding backbone hydrogen bonds takes place during protein folding as hydrophobic residues cluster around such bonds. Taken as an average over all hydrogen bonds, the extent of desolvation is nearly a constant of motion, as revealed by re-examination of the longest all-atom trajectory with explicit solvent [Y. Duan & P. A. Kollman (1998) Science 282, 740]. Furthermore, this extent of desolvation is preserved across native soluble proteins, except for cellular prion proteins. Thus, a physico-chemical picture of prion-related disease emerges. The epitope for protein-X binding, the region undergoing vast conformational change and the trigger and locker for this change are inferred from the location of under-desolvated hydrogen bonds in the cellular prion protein.
在蛋白质折叠过程中，随着疏水残基聚集在主链氢键周围，会发生围绕主链氢键的水的结构化及最终排除。通过重新审视含有明确溶剂的最长全原子轨迹发现，就所有氢键的平均值而言，去溶剂化程度几乎是一个运动常数[Y. 段 & P. A. 科尔曼（1998年）《科学》282卷，第740页]。此外，除了细胞朊病毒蛋白外，这种去溶剂化程度在天然可溶性蛋白中是保持不变的。因此，一种与朊病毒相关疾病的物理化学图景浮现出来。从细胞朊病毒蛋白中去溶剂化不足的氢键位置，可以推断出与蛋白X结合的表位、经历巨大构象变化的区域以及这种变化的触发因素和锁定因素。
