Molecular Dynamics Insight into the Diverse Thermodynamic Behavior of a Beta‐Hairpin Peptide

Tsai, Ming-Yen; Yuan, Jian Min; Yamaki, Masahiro; Lin, Ching‐Fuh; Lin, Sheng Hsien

doi:10.1002/jccs.201300173

Cited by 1 publication

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteins contain several types of side chain residues that are intrinsic fluorophores in the context of the protein environment. Among these photoactive residues, tryptophan represents the most popular one due to its wide use in probing folding [1][2][3][4][5] and binding [3,6] as well as many biomedical applications. [7] The conformational isomers of tryptophan in the gas phase have been computationally studied.…”

Section: Introductionmentioning

confidence: 99%

A generic rotamer model to explain the temperature dependence of BSA protein fluorescence

Chou

Lin

Tsai

2023

J Chinese Chemical Soc

Self Cite

View full text Add to dashboard Cite

Protein fluorescence signals essential information about the conformational dynamics of proteins. Different types of intrinsic fluorophores reflect different protein local or global structural changes. Bovine Serum Albumin (BSA) is a transport protein that contains two intrinsic fluorophores: Tryptophan134 (Trp134) and Tryptophan213 (Trp213). This protein displays an interesting temperature dependence of the tryptophan fluorescence. However, the molecular mechanism of the temperature dependence is still unclear. In this work, we propose a generic rotamer model to explain this phenomenon. The model assumes the presence of rotamer‐specific fluorescence lifetimes. The fluorescence temperature dependence is caused by the population shifts between different rotamers due to thermal effects. As a proof of concept, we show that the tryptophan's two fluorescence lifetimes (𝜏1 = 0.4–0.5 ns and 𝜏2 = 2‐4 ns) are sufficient to qualitatively explain the fluorescence intensity change at different temperatures, both in buffer solution (water) and in the protein. To computationally verify our rotamer hypothesis, we use an all‐atom molecular dynamics simulation to study the effects of temperature on the two tryptophans' rotamer dynamics. The simulations show that Trp134 is more sensitive to temperature, consistent with experimental observations. Overall, the results support that the temperature dependence of fluorescence in the protein BSA is due to local conformational changes at the residue level. This work sheds light on the relationship between tryptophan's rotamer dynamics and its ability to fluorescence.

show abstract