Molecular dynamics simulations of G-quadruplexes: The basic principles and their application to folding and ligand binding
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00540713" target="_blank" >RIV/68081707:_____/20:00540713 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0065774320300154?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0065774320300154?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/bs.armc.2020.04.002" target="_blank" >10.1016/bs.armc.2020.04.002</a>
Alternative languages
Result language
angličtina
Original language name
Molecular dynamics simulations of G-quadruplexes: The basic principles and their application to folding and ligand binding
Original language description
Current state-of-the art explicit-solvent atomistic molecular dynamics (MD) simulations are reviewed. We describe the basic principles and limitations of MD methodology. We also explain how to compare MD simulations with experiments and how to correctly interpret MD data. Different types of simulation approaches are introduced. We start with standard simulations and then continue with techniques which allow one to a certain extent overcome sampling limitations and derive free energies: replica-exchange methods, collective-variable based methods such as metadynamics, alchemical methods, Markov state models and continuum solvent approach. We emphasize explaining the limitations of the methods, in order to avoid over-interpretation of the simulation data. Then we introduce recent progress in the force fields that are used for simulations of quadruplexes. Finally, two specific areas are reviewed. First, we explain how MD simulations are essential to unravel the uniqueness and complexity of quadruplex folding landscape, what are the basic consequences and hallmarks of kinetic partitioning of the landscape and why low-dimensionality descriptions (both experimental and computational) can easily lead to major oversimplifications. Second, MD simulations-based recent approaches to probe quadruplex-ligand interactions are discussed. The review is primarily written for readers who are not advanced experts in MD simulations, with the aim to openly expose their limitations.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Structural gymnastics of nucleic acids: from molecular principles through biological functions to therapeutic targets.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Annual Reports in Medicinal Chemistry
ISSN
0065-7743
e-ISSN
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Volume of the periodical
54
Issue of the periodical within the volume
2020
Country of publishing house
GB - UNITED KINGDOM
Number of pages
45
Pages from-to
197-241
UT code for WoS article
000611825800009
EID of the result in the Scopus database
2-s2.0-85088926605