AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00501431" target="_blank" >RIV/61388963:_____/19:00501431 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.8b00715" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.8b00715</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.8b00715" target="_blank" >10.1021/acs.jctc.8b00715</a>

Result language

angličtina

Original language name

AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation

Original language description

Phosphorylation of serine, threonine, and tyrosine is one of the most frequently occurring and crucial post-translational modifications of proteins often associated with important structural and functional changes. We investigated the direct effect of phosphorylation on the intrinsic conformational preferences of amino acids as a potential trigger of larger structural events. We conducted a comparative study of force fields on terminally capped amino acids (dipeptides) as the simplest model for phosphorylation. Our bias-exchange metadynamics simulations revealed that all model dipeptides sampled a great heterogeneity of ensembles affected by introduction of mono- and dianionic phosphate groups. However, the detected changes in populations of backbone conformers and side-chain rotamers did not reveal a strong discriminatory shift in preferences, as could be anticipated for the bulky, charged phosphate group. Furthermore, the AMBER and CHARMM force fields provided inconsistent populations of individual conformers as well as net structural trends upon phosphorylation. Detailed analysis of ensembles revealed competition between hydration and formation of internal hydrogen bonds involving amide hydrogens and the phosphate group. The observed difference in hydration free energy and potential for hydrogen bonding in individual force fields could be attributed to the different partial atomic charges used in each force field and, hence, the different parametrization strategies. Nevertheless, conformational propensities and net structural changes upon phosphorylation are difficult to extract from experimental measurements, and existing experimental data provide limited guidance for force field assessment and further development.

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

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OECD FORD branch

10403 - Physical chemistry

Project

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

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

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

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

665-679

UT code for WoS article

000455558200058

EID of the result in the Scopus database

2-s2.0-85058544605