Cosolvent Exclusion Drives Protein Stability in Trimethylamine N-Oxide and Betaine Solutions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00561273" target="_blank" >RIV/61388963:_____/22:00561273 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22340/22:43924997

Result on the web

<a href="https://doi.org/10.1021/acs.jpclett.2c01692" target="_blank" >https://doi.org/10.1021/acs.jpclett.2c01692</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpclett.2c01692" target="_blank" >10.1021/acs.jpclett.2c01692</a>

Result language

angličtina

Original language name

Cosolvent Exclusion Drives Protein Stability in Trimethylamine N-Oxide and Betaine Solutions

Original language description

Using a combination of molecular dynamics simulation, dialysis experiments, and electronic circular dichroism measurements, we studied the solvation thermodynamics of proteins in two osmolyte solutions, trimethylamine N-oxide (TMAO) and betaine. We showed that existing force fields are unable to capture the solvation properties of the proteins lysozyme and ribonuclease T1 and that the inaccurate parametrization of protein-osmolyte interactions in these force fields promoted an unphysical strong thermal denaturation of the trpcage protein. We developed a novel force field for betaine (the KBB force field) which reproduces the experimental solution Kirkwood-Buff integrals and density. We further introduced appropriate scaling to protein-osmolyte interactions in both the betaine and TMAO force fields which led to successful reproduction of experimental protein-osmolyte preferential binding coefficients for lysozyme and ribonuclease T1 and prevention of the unphysical denaturation of trpcage in osmolyte solutions. Correct parametrization of protein-TMAO interactions also led to the stabilization of the collapsed conformations of a disordered elastin-like peptide, while the uncorrected parameters destabilized the collapsed structures. Our results establish that the thermodynamic stability of proteins in both betaine and TMAO solutions is governed by osmolyte exclusion from proteins.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Physical Chemistry Letters

ISSN

1948-7185

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

34

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

7980-7986

UT code for WoS article

000864672500001

EID of the result in the Scopus database

2-s2.0-85137136902