Department of Chemistry , Georgetown University , Washington, D.C. 20057 , United States.
J Phys Chem B. 2019 Feb 7;123(5):1108-1115. doi: 10.1021/acs.jpcb.8b09874. Epub 2019 Jan 28.
Trimethylamine N-oxide (TMAO) stabilizes protein structures, whereas urea destabilizes proteins, and their opposing effects can be counteracted at a 1:2 ratio of TMAO to urea. To investigate how they affect solution dynamics, molecular dynamics simulations have been carried out for aqueous solutions of TMAO and urea at different concentrations. In the binary solutions, urea mainly slows the diffusion of waters that are hydrogen bonded to it (i.e., hydration water), whereas TMAO dramatically slows the diffusion of both hydration water and bulk water because of long-lived TMAO-water hydrogen bonds. In the ternary solutions, because TMAO decreases the diffusion rate of bulk water, the lifetimes of not only water-water but also urea-water hydrogen bonds increase. In addition, the constant forming and breaking of short lifetime hydrogen bonds between urea and water appears to impart energy into the bulk, whereas the long lifetime hydrogen bonds between TMAO and water slows down the bulk, resulting in the compensating effects on bulk water in the ternary solution. This suggests that the counteracting effects of TMAO on urea denaturation may be both to make longer lived hydrogen bonds to water and to counter the energizing effects of urea on bulk water.
三甲基胺 N-氧化物（TMAO）稳定蛋白质结构，而尿素使蛋白质不稳定，它们的相反作用可以在 TMAO 与尿素 1:2 的比例下相互抵消。为了研究它们如何影响溶液动力学，对不同浓度的 TMAO 和尿素的水溶液进行了分子动力学模拟。在二元溶液中，尿素主要减缓与其氢键合的水（即水合水）的扩散，而 TMAO 由于长寿命的 TMAO-水氢键，极大地减缓了水合水和体相水的扩散。在三元溶液中，由于 TMAO 降低了体相水的扩散速率，不仅水-水氢键，而且尿素-水氢键的寿命增加。此外，尿素和水之间短寿命氢键的不断形成和断裂似乎将能量传递到体相，而 TMAO 和水之间长寿命氢键使体相减速，从而在三元溶液中对体相水产生补偿效应。这表明 TMAO 对尿素变性的拮抗作用可能是形成更长寿命的氢键以水合，并抵消尿素对体相水的增能作用。
