PMID- 34926581
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211221
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent 
      Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and 
      Stability.
PG  - 778244
LID - 10.3389/fmolb.2021.778244 [doi]
LID - 778244
AB  - 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.
CI  - Copyright (c) 2021 Kwok, Camacho, Winter, Knight, Meade, Van der Kamp, Turner, 
      O'Hara, Mason, Jones, Arcus and Pudney.
FAU - Kwok, A
AU  - Kwok A
AD  - Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
FAU - Camacho, I S
AU  - Camacho IS
AD  - Biometrology, Chemical and Biological Sciences Department, National Physical 
      Laboratory, London, United Kingdom.
FAU - Winter, S
AU  - Winter S
AD  - Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
FAU - Knight, M
AU  - Knight M
AD  - UCB, Slough, United Kingdom.
FAU - Meade, R M
AU  - Meade RM
AD  - Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
FAU - Van der Kamp, M W
AU  - Van der Kamp MW
AD  - School of Biochemistry, University of Bristol, Bristol, United Kingdom.
FAU - Turner, A
AU  - Turner A
AD  - UCB, Slough, United Kingdom.
FAU - O'Hara, J
AU  - O'Hara J
AD  - UCB, Slough, United Kingdom.
FAU - Mason, J M
AU  - Mason JM
AD  - Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
FAU - Jones, A R
AU  - Jones AR
AD  - Biometrology, Chemical and Biological Sciences Department, National Physical 
      Laboratory, London, United Kingdom.
FAU - Arcus, V L
AU  - Arcus VL
AD  - School of Science, Faculty of Science and Engineering, University of Waikato, 
      Hamilton, New Zealand.
FAU - Pudney, C R
AU  - Pudney CR
AD  - Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
AD  - BLOC Laboratories Limited, Bath, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20211203
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8681860
OTO - NOTNLM
OT  - conformational sampling
OT  - fluorescence
OT  - protein stability
OT  - red edge excitation shift
OT  - tryptophan
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/21 06:00
MHDA- 2021/12/21 06:01
PMCR- 2021/01/01
CRDT- 2021/12/20 06:18
PHST- 2021/09/16 00:00 [received]
PHST- 2021/10/27 00:00 [accepted]
PHST- 2021/12/20 06:18 [entrez]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2021/12/21 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 778244 [pii]
AID - 10.3389/fmolb.2021.778244 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Dec 3;8:778244. doi: 10.3389/fmolb.2021.778244. 
      eCollection 2021.