A5018229309- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Photochromic and Fluorescence Chemistry
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Molecular Junctions and Nanostructures
- RNA Interference and Gene Delivery
- Graphene research and applications
- Computational Drug Discovery Methods
- Crystallography and molecular interactions
- Surface Chemistry and Catalysis
- Advanced Chemical Physics Studies
- Bacteriophages and microbial interactions
- Chronic Myeloid Leukemia Treatments
- Protein purification and stability
- Chemical Synthesis and Analysis
- Metal complexes synthesis and properties
- Monoclonal and Polyclonal Antibodies Research
- Quinazolinone synthesis and applications
- Biochemical effects in animals
- Molecular Spectroscopy and Structure
- RNA Research and Splicing
- Spectroscopy and Quantum Chemical Studies
- RNA modifications and cancer
- Various Chemistry Research Topics
University of Bristol
2018-2022
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2012-2017
Regional Centre of Advanced Technologies and Materials
2016
Palacký University Olomouc
2016
Charles University
2012-2015
Czech Academy of Sciences
2015
The cationic porphyrin TMPyP4 is a well-established DNA G-quadruplex (G4) binding ligand that can stabilize different topologies via multiple modes. However, have both stabilizing and destabilizing effect on RNA G4 structures. structural mechanisms mediate unfolding remain unknown. Here, we report the TMPyP4-induced mechanism studied by well-tempered metadynamics (WT-MetaD) with supporting biophysical experiments. simulations predict two-state of interaction groove-bound top-face-bound...
Abstract The polymorphic nature of G‐quadruplex (G4) DNA structures points to a range potential applications in nanodevices and an opportunity control G4 biological settings. Light is attractive means for the regulation oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards development ligands that allow photoregulation folding. We report novel G4‐binding chemotype derived from stiff‐stilbene....
RNA hairpins capped by 5'-GNRA-3' or 5'-UNCG-3' tetraloops (TLs) are prominent structural motifs. Despite their small size, a wealth of experimental data, and recent progress in theoretical simulations dynamics folding, our understanding the folding unfolding processes these elements is still limited. Theoretical description requires robust sampling, which can be achieved either an exhaustive time scale standard molecular sophisticated enhanced sampling methods, using temperature...
The effect of halogen-to-hydrogen bond substitution on the binding energetics and biological activity a human aldose reductase inhibitor has been studied using X-ray crystallography, IC50 measurements, advanced free energy calculations, simulations. replacement Br or I atoms by an amine (NH2) group not induced changes in original geometry complex, which made it possible to study isolated features selected noncovalent interactions biomolecular complex.
A pyridinium-decorated photoresponsive dithienylethene selectively targets G-quadruplex DNA, allowing binding mode and toxicity to be controlled exclusively with visible light.
Drug-target binding kinetics has recently emerged as a sometimes critical determinant of in vivo efficacy and toxicity. Its rational optimization to improve potency or reduce side effects drugs is, however, extremely difficult. Molecular simulations can play crucial role identifying features properties small ligands their protein targets affecting the kinetics, but significant challenges include long time scales involved (un)binding events limited accuracy empirical atomistic force fields...
Ligands with the capability to bind G-quadruplexes (G4s) specifically, and control G4 structure behaviour, offer great potential in development of novel therapies, technologies functional materials. Most known ligands a pre-formed topology, but G4s are highly dynamic small number have been discovered that influence these folding equilibria. Such may be useful as probes understand nature vivo, or exploit polymorphism molecular devices. To date, fascinating molecules serendipitously. There is...
General and reliable description of structures energetics in protein-ligand (PL) binding using the docking/scoring methodology has until now been elusive. We address this urgent deficiency scoring functions (SFs) by systematic development corrected semiempirical quantum mechanical (SQM) methods, which correctly describe all types noncovalent interactions are fast enough to treat systems thousands atoms. Two most accurate SQM PM6-D3H4X SCC-DFTB3-D3H4X, coupled with conductor-like screening...
Various cluster models of graphene and a periodic with two organic electron acceptors (tetracyanoethylene tetracyanoquinodimethane) were investigated by means several quantum chemical molecular mechanical approaches. The benchmark interaction energies the coronene complexes calculated at MP2.5/CBS/6-31G*(0.25) level theory. SCS-MI-MP2, BLYP-D3 and, surprisingly, also AMBER showed modest agreement in absolute as well relative energies. Consequently, larger these lower levels theory including...
Dissociation energies (D0) of 11 H-bonded and dispersion-bound complexes were calculated as the sum interaction change zero-point vibrational (ΔZPVE). The structures optimized at RI-MP2/cc-pVTZ level, which deformation harmonic ΔZPVE also calculated. DFT-D3 determined same level well. For comparison, CCSD(T)/CBS D0 evaluated for both types complexes. energy was constructed MP2/CBS energy, extrapolated from aug-cc-pVTZ aug-cc-pVQZ basis sets, ΔCCSD(T) correction, with aug-cc-pVDZ set. all...
Abstract The polymorphic nature of G‐quadruplex (G4) DNA structures points to a range potential applications in nanodevices and an opportunity control G4 biological settings. Light is attractive means for the regulation oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards development ligands that allow photoregulation folding. We report novel G4‐binding chemotype derived from stiff‐stilbene....
The adsorption of the DNA bases and base pairs on hydrophobic silica surface has been investigated by ab initio quantum mechanical (QM) methods (DFT–D) molecular mechanics (MM) also biased dynamics (MD) simulations (metadynamics). structures all clusters (surface with single-bases pairs) predicted means force field are compared results direct QM calculations. MM interaction energies for agreed well ones, which justifies use in evaluation accurate free energies. Rigid rotor–harmonic...
Graphene and its derivatives are useful building blocks for the bottom-up assembly of advanced functional materials. Noncovalently functionalized graphene networks offer a wide range applications. We investigated formation sandwich-like three-layered nanostructures with graphene. Novel architectures have been generated by stacking selected suitable organic molecules based on their characterized donor acceptor strengths vertically surface. This paper describes adsorption electron-acceptor...
The ability to control G-quadruplex (G4) conformation using light as an external stimuli offers unique opportunities G4 in biological settings and for the development of nucleotide-based nanodevices. We describe a novel G4-binding chemotype derived from cyclic azobenzene core that reversibly photoisomerises between E- Z- under physiological conditions. demonstrate selective binding E-ligand towards LTR-III show dissociation can be controlled by alternate irradiation with blue green light....
Abstract The cationic porphyrin, TMPyP4, is a well-established DNA G-quadruplex (G4) binding ligand that can stabilize different topologies via multiple modes. However, TMPyP4 has completely opposite destabilizing and unwinding effect on RNA G4 structures. structural mechanisms mediate unfolding remains unknown. Here, we report the TMPyP4-induced mechanism studied by well-tempered metadynamics (WT-MetaD) with supporting biophysical experiments. simulations predict two-state of interaction...
Photoresponsive ligands for G-quadruplex oligonucleotides (G4) offer exciting opportunities the reversible regulation of these assemblies with potential applications in biological chemistry and responsive nanotechnology. However, achieving robust G4 ligand activity low-energy visible light sources that are easily accessible compatible systems remains a significant challenge to realizing applications. Herein, we report G4-binding properties photoresponsive dithienylethene (DTE). We...
<div><p>Photoresponsive ligands for G-quadruplex oligonucleotides (G4) offer exciting opportunities the reversible regulation of these assemblies with potential applications in biological chemistry and responsive nanotechnology. However, achieving robust G4 ligand activity low-energy visible light sources that are easily accessible compatible systems remains a significant challenge to realizing applications. Herein, we report G4-binding properties photoresponsive dithienylethene...
Photoresponsive ligands for G-quadruplex oligonucleotides (G4) offer exciting opportunities the reversible regulation of these assemblies with potential applications in biological chemistry and responsive nanotechnology. However, achieving robust G4 ligand activity low-energy visible light sources that are easily accessible compatible systems remains a significant challenge to realizing applications. Herein, we report G4-binding properties photoresponsive dithienylethene (DTE). We...