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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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Autores principales: Kwok, A, Camacho, IS, Winter, S, Knight, M, Meade, RM, Van der Kamp, MW, Turner, A, O’Hara, J, Mason, JM, Jones, AR, Arcus, VL, Pudney, CR
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8681860/
https://www.ncbi.nlm.nih.gov/pubmed/34926581
http://dx.doi.org/10.3389/fmolb.2021.778244
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author Kwok, A
Camacho, IS
Winter, S
Knight, M
Meade, RM
Van der Kamp, MW
Turner, A
O’Hara, J
Mason, JM
Jones, AR
Arcus, VL
Pudney, CR
author_facet Kwok, A
Camacho, IS
Winter, S
Knight, M
Meade, RM
Van der Kamp, MW
Turner, A
O’Hara, J
Mason, JM
Jones, AR
Arcus, VL
Pudney, CR
author_sort Kwok, A
collection PubMed
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.
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spelling pubmed-86818602021-12-18 A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability Kwok, A Camacho, IS Winter, S Knight, M Meade, RM Van der Kamp, MW Turner, A O’Hara, J Mason, JM Jones, AR Arcus, VL Pudney, CR Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2021-12-03 /pmc/articles/PMC8681860/ /pubmed/34926581 http://dx.doi.org/10.3389/fmolb.2021.778244 Text en Copyright © 2021 Kwok, Camacho, Winter, Knight, Meade, Van der Kamp, Turner, O’Hara, Mason, Jones, Arcus and Pudney. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Kwok, A
Camacho, IS
Winter, S
Knight, M
Meade, RM
Van der Kamp, MW
Turner, A
O’Hara, J
Mason, JM
Jones, AR
Arcus, VL
Pudney, CR
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability
title 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_short 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
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8681860/
https://www.ncbi.nlm.nih.gov/pubmed/34926581
http://dx.doi.org/10.3389/fmolb.2021.778244
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