What can we learn from transition path time distributions for protein folding and unfolding?
Phys Chem Chem Phys
; 23(41): 23787-23795, 2021 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-34643635
ABSTRACT
Recent advances in experimental measurements of transition path time distributions have raised intriguing theoretical questions. The present interpretation of the experimental data indicates a small value of the fitted transition path barrier height as compared to the barrier height of the unfolded to folded transition. Secondly, as shown in this paper, it is essential to analyse the experimental data using absorbing boundary conditions at the end points used to determine the transition paths. Such an analysis reveals long time tails that have thus far eluded quantitative theoretical interpretation. Is this due to uncertainty in the experimental data or does it call for a rethinking of the theoretical interpretation? A detailed study of the transition path time distribution using a diffusive model leads to the following conclusions. a. The present experimental data is not accurate enough to discern between functional forms of bell shaped free energy barriers. b. Long time tails indicate the possible existence of a "trap" in the transition path region. c. The "trap" may be considered as a well in the free energy surface. d. The long time tail is quite sensitive to the form of the trap so that future measurements of the long time tail as a function of the location of the end points of the transition path may make it possible to not only determine the well depth but also to distinguish between different functional forms for the free energy surface. e. Introduction of a well along the transition path leads to good fits with the experimental data provided that the transition path barrier height is â¼3kBT, substantially higher than the estimates of â¼1kBT based on bell shaped functions. The results presented here negate the need of introducing multi-dimensional effects, free energy barrier asymmetry, sub-diffusive memory kernels or systematic ruggedness to explain the experimentally measured data.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Desdobramento de Proteína
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Phys Chem Chem Phys
Assunto da revista:
BIOFISICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Israel
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
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UNITED KINGDOM