A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability
It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quant...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:1439860014ea47359cd6861b3f8b4edf2021-12-03T16:46:19ZA Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability2296-889X10.3389/fmolb.2021.778244https://doaj.org/article/1439860014ea47359cd6861b3f8b4edf2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.778244/fullhttps://doaj.org/toc/2296-889XIt is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.A KwokIS CamachoS WinterM KnightRM MeadeMW Van der KampA TurnerJ O’HaraJM MasonAR JonesVL ArcusCR PudneyCR PudneyFrontiers Media S.A.articleprotein stabilityred edge excitation shiftfluorescencetryptophanconformational samplingBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021) |
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DOAJ |
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protein stability red edge excitation shift fluorescence tryptophan conformational sampling Biology (General) QH301-705.5 |
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protein stability red edge excitation shift fluorescence tryptophan conformational sampling Biology (General) QH301-705.5 A Kwok IS Camacho S Winter M Knight RM Meade MW Van der Kamp A Turner J O’Hara JM Mason AR Jones VL Arcus CR Pudney CR Pudney A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| description |
It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights. |
| format |
article |
| author |
A Kwok IS Camacho S Winter M Knight RM Meade MW Van der Kamp A Turner J O’Hara JM Mason AR Jones VL Arcus CR Pudney CR Pudney |
| author_facet |
A Kwok IS Camacho S Winter M Knight RM Meade MW Van der Kamp A Turner J O’Hara JM Mason AR Jones VL Arcus CR Pudney CR Pudney |
| author_sort |
A Kwok |
| title |
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| title_short |
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| title_full |
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| title_fullStr |
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| title_full_unstemmed |
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability |
| title_sort |
thermodynamic model for interpreting tryptophan excitation-energy-dependent fluorescence spectra provides insight into protein conformational sampling and stability |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/1439860014ea47359cd6861b3f8b4edf |
| work_keys_str_mv |
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