Trimethylamine N-oxide (TMAO) stabilizes the native state of globular proteins and counteracts the destabilizing action of denaturants. However, at pH values lower than its pKa = 4.7, TMAO destabilizes the native state. We studied, via DFT calculations, the interactions of TMAO, its protonated form and isosteric tert-butanol with one, two and three water molecules in vacuo, PCM and SMD water. The energetic strength of the H-bonds the considered solutes make with three water molecules, coupled to a model of globular protein stability, allows us to propose a rationalization of the pH-dependent TMAO behavior toward globular proteins.
A quantum chemical study on the hydration energetics of trimethylamine N-oxide, its protonated form and tert-butanol / Crescenzi, O.; Graziano, G.. - In: CHEMICAL PHYSICS LETTERS. - ISSN 0009-2614. - 804:(2022), p. 139905. [10.1016/j.cplett.2022.139905]
A quantum chemical study on the hydration energetics of trimethylamine N-oxide, its protonated form and tert-butanol
Crescenzi O.;
2022
Abstract
Trimethylamine N-oxide (TMAO) stabilizes the native state of globular proteins and counteracts the destabilizing action of denaturants. However, at pH values lower than its pKa = 4.7, TMAO destabilizes the native state. We studied, via DFT calculations, the interactions of TMAO, its protonated form and isosteric tert-butanol with one, two and three water molecules in vacuo, PCM and SMD water. The energetic strength of the H-bonds the considered solutes make with three water molecules, coupled to a model of globular protein stability, allows us to propose a rationalization of the pH-dependent TMAO behavior toward globular proteins.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
