MD and QM/MM Study of the Quaternary HutP Homohexamer Complex with mRNA, L-Histidine Ligand, and Mg2+
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00486064" target="_blank" >RIV/68081707:_____/17:00486064 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/17:73584576
Result on the web
<a href="http://dx.doi.org/10.1021/acs.jctc.7b00598" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.7b00598</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.7b00598" target="_blank" >10.1021/acs.jctc.7b00598</a>
Alternative languages
Result language
angličtina
Original language name
MD and QM/MM Study of the Quaternary HutP Homohexamer Complex with mRNA, L-Histidine Ligand, and Mg2+
Original language description
The HutP protein from B. subtilis regulates histidine metabolism by interacting with an antiterminator mRNA hairpin in response to the binding of L-histidine and Mg2+. We studied the functional ligand-bound HutP hexamer complexed with two mRNAs using all-atom microsecond-scale explicit-solvent MD simulations performed with the Amber force fields. The experimentally observed protein-RNA interface exhibited good structural stability in the simulations with the exception of some fluctuations in an unusual adenine-threonine interaction involving two closely spaced H-bonds. We further investigated this interaction by comparing QM/MM and MM optimizations, using the QM region comprising almost 350 atoms described at the DFT-D3 level. The QM/MM method clearly improved the adenine-threonine interaction compared to MM, especially when the X H bond lengths were frozen during the MM optimization to mimic the use of SHAKE in the MD simulations. Thus, both the MM approximation and the use of SHAKE can compromise the description of H-bonds at protein RNA interfaces. The simulations also revealed a notable Mg2+-parameter dependence in the behavior of the ligand-binding pocket (LBP). With the SPC/E water model, the 12-6 Aqvist and Li&Merz parameters provided an entirely stable LBP structure, but the 12-6 Allner and 12-6-4 Li&Merz parametrizations resulted in a progressive loss of direct nitrogen Mg2+ LBP coordination. The Aliner and Li&Merz 12-6 parametrizations were also tested with the TIP3P water model, the LBP was destabilized in both cases. This illustrates the difficulty of consistently describing different Mg2+ interactions using nonpolarizable force fields. Overall, the simulations support the hypothesis that HutP protein becomes fully structured upon ligand binding. Subsequent RNA binding does not affect the protein structure, in keeping with the mechanism inferred from experimental structures.
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
2017
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
13
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
5658-5670
UT code for WoS article
000415911800042
EID of the result in the Scopus database
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