AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation
The result's identifiers
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>
Alternative languages
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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Classification
Type
J<sub>imp</sub> - 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
Result continuities
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)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Chemical Theory and Computation
ISSN
1549-9618
e-ISSN
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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