Folding of guanine quadruplex molecules-funnel-like mechanism or kinetic partitioning? An overview from MD simulation studies.

  title={Folding of guanine quadruplex molecules-funnel-like mechanism or kinetic partitioning? An overview from MD simulation studies.},
  author={Jiřı {\vS}poner and Giovanni Bussi and Petr Stadlbauer and Petra K{\"u}hrov{\'a} and Pavel Ban{\'a}{\vs} and Barira Islam and Shozeb M. Haider and Stephen Neidle and Michal Otyepka},
  journal={Biochimica et biophysica acta. General subjects},
  volume={1861 5 Pt B},

Structural dynamics of propeller loop: towards folding of RNA G-quadruplex

It is suggested that CS and PH-types of structures are sufficiently populated during RNA guanine quadruplex (GQ) folding within the context of complete GQ-forming sequences.

In silico direct folding of thrombin-binding aptamer G-quadruplex at all-atom level

From this direct folding simulation using the modified bsc1 force field, reasonably converged free energy landscapes were obtained in K+-rich aqueous solution, providing detailed atomistic pictures of GQ folding mechanisms for TBA-15.

Insights into the kinetic partitioning folding dynamics of human telomeric G-quadruplex from molecular simulations and machine learning.

A hybrid atomistic structure-based model that merges structural information on the hybrid-1, hybrid-2 and chair-type G-quadruplex topologies and coupling the multi-basin model and the machine learning algorithm may be useful to investigate the conformational dynamics of other multistate biomolecules.

Folding dynamics of polymorphic G‐quadruplex structures

Recent experimental approaches to monitor G4 folding are reviewed, structural aspects for possible folding pathways are discussed and comprehensive models of the complex folding energy landscape of G4s are evaluated based on computational and experimental evidence.

Insights into G-Quadruplex–Hemin Dynamics Using Atomistic Simulations: Implications for Reactivity and Folding

Extended explicit-solvent molecular dynamics simulations are used to scrutinize the G4/hemin interaction and suggest tentative mechanisms in which the external G-quartet itself is responsible for the unique H2O2-promoted biocatalytic properties of the G 4/ hemin complexes.

Pre-folded structures govern folding pathways of human telomeric G-quadruplexes

Varying the pH and temperature by the use of nuclear magnetic resonance and other methods enabled detection of pre-folded structures that exist in solution before completely formed G-quadruplexes upon addition of cations and revealed one common structural feature that could govern folding process.

Parallel G-triplexes and G-hairpins as potential transitory ensembles in the folding of parallel-stranded DNA G-Quadruplexes

The parallel G-triplex is a possible, but not mandatory short-living (transitory) intermediate in the folding of parallel-stranded G4, thus providing atomistic level of description of the single-molecule folding events.

Conformational Dynamics of Strand Register Shifts in DNA G-quadruplexes.

This work studied two different G-quadruplexes, selecting a single conformation by blocking hydrogen bonding with photolabile protection groups and compared the NMR-derived refolding kinetics with data derived from thermal hysteresis folding kinetic experiments and found excellent agreement.



Coarse-Grained Simulations Complemented by Atomistic Molecular Dynamics Provide New Insights into Folding and Unfolding of Human Telomeric G-Quadruplexes.

The inability of simple order parameters, such as radius of gyration or the number of native H-bonds, to describe the folding landscape of the G-quadruplexes is demonstrated, which indicates how various pathways are interconnected in a complex network.

Hairpins participating in folding of human telomeric sequence quadruplexes studied by standard and T-REMD simulations

The simulations strongly suggest that the GQ folding could be best understood by the kinetic partitioning mechanism with a set of deep competing minima on the folding landscape, with only a small fraction of molecules directly folding to the native fold.

A direct view of the complex multi-pathway folding of telomeric G-quadruplexes

This work employs single-molecule FRET microscopy to obtain a direct view of the folding and underlying conformational dynamics of G4s formed by the human telomeric sequence in potassium containing solutions and provides a comprehensive thermodynamic and kinetic description of the fold of G 4s that proceeds through a complex multi-route pathway.

Folding dynamics and conformational heterogeneity of human telomeric G-quadruplex structures in Na+ solutions by single molecule FRET microscopy

This work investigated telomeric G-quadruplex folding using single molecule FRET microscopy in conditions where it was previously believed to yield low structural heterogeneity, and observed four FRET states in Na+ buffers: an unfolded state and three G-squared related states that can interconvert between each other.

The kinetics and folding pathways of intramolecular G-quadruplex nucleic acids.

The findings suggest a folding mechanism that involves two kinetic steps with initial binding of a single K(+), irrespective of the number of G-quartets involved or whether the G-quadruplex is formed from RNA or DNA.

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model

It is revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates, and another intermediate state was identified, which exhibits higher population and stability than the G-triplex-like intermediate.

Computational Insights into the Stability and Folding Pathways of Human Telomeric DNA G-Quadruplexes.

  • D. LuoY. Mu
  • Chemistry
    The journal of physical chemistry. B
  • 2016
The stability and folding dynamics of human telomeric DNA G-quadruplexes were investigated via enhanced sampling techniques and it was observed that the N-glycosidic conformations of guanines can flip over to accommodate into the cyclic Hoogsteen H-bonding on G-tetrads in which they were not originally involved.

Folding and unfolding pathways of the human telomeric G-quadruplex.

G-quadruplex conformation and dynamics are determined by loop length and sequence

It is demonstrated that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation.

Folding pathways of human telomeric type-1 and type-2 G-quadruplex structures.

The results suggest the formation of type-1 and type-2 G-quadruplex structures with the possibility of hairpin and triplex intermediates, and the K(+) binding to a hairpin near the second lateral TTA loop was found to be preferable, considering entropic effects.