QM/MM Calculations on Protein-RNA Complexes: Understanding Limitations of Classical MD Simulations and Search for Reliable Cost-Effective QM Methods
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00101368" target="_blank" >RIV/00216224:14740/18:00101368 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/18:00502400
Result on the web
<a href="http://dx.doi.org/10.1021/acs.jctc.8b00670" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.8b00670</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.8b00670" target="_blank" >10.1021/acs.jctc.8b00670</a>
Alternative languages
Result language
angličtina
Original language name
QM/MM Calculations on Protein-RNA Complexes: Understanding Limitations of Classical MD Simulations and Search for Reliable Cost-Effective QM Methods
Original language description
Although atomistic explicit-solvent Molecular Dynamics (MD) is a popular tool to study protein-RNA recognition, satisfactory MD description of protein-RNA complexes is not always achieved. Unfortunately, it is often difficult to separate MD simulation instabilities primarily caused by the simple point-charge molecular mechanics (MM) force fields from problems related to the notorious uncertainties in the starting structures. Herein, we report a series of large-scale QM/MM calculations on the U1A protein-RNA complex. This experimentally well-characterized system has an intricate protein-RNA interface, which is very unstable in MD simulations. The QM/MM calculations identify several H-bonds poorly described by the MM method and thus indicate the sources of instabilities of the U1A interface in MD simulations. The results suggest that advanced QM/MM computations could be used to indirectly rationalize problems seen in MM-based MD simulations of protein-RNA complexes. As the most accurate QM method, we employ the computationally demanding meta-GGA density functional TPSS-D3(BJ)/def2-TZVP level of theory. Because considerably faster methods would be needed to extend sampling and to study even larger protein-RNA interfaces, a set of low-cost QM/MM methods is compared to the TPSS-D3(BJ)/def2-TZVP data. The PBEh-3c and B97-3c density functional composite methods appear to be suitable for protein-RNA interfaces. In contrast, HF-3c and the tight-binding Hamiltonians DFTB3-D3 and GFN-xTB perform unsatisfactorily and do not provide any advantage over the MM description. These conclusions are supported also by similar analysis of a simple HutP protein-RNA interface, which is well-described by MD with the exception of just one H-bond. Some other methodological aspects of QM/MM calculations on protein-RNA interfaces are discussed.
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
2018
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
14
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
5419-5433
UT code for WoS article
000447238500037
EID of the result in the Scopus database
2-s2.0-85054171439