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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/60461373:22340/22:43924997

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

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

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry Letters

ISSN

1948-7185

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

34

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

7980-7986

Kód UT WoS článku

000864672500001

EID výsledku v databázi Scopus

2-s2.0-85137136902