Biology subjects

Matouskova, E.

Publications and source records attributed to Matouskova, E..

5 recordsLinked to original sources

bioRxiv2026

Mechanical properties of DNA double-crossover motifs

DNA double-crossover (DX) molecules, comprising two Holliday junctions connected by two duplex arms, are fundamental building blocks of DNA nanostructures, but their mechanical properties remain poorly understood. Here we investigate the elasticity of isolated antiparallel DX motifs with 18 to 22 base pairs between the crossovers. Using mechanical models parameterized by extensive all-atom molecular dynamics simulations, we demonstrate that the bending rigidity of the duplexes within a DX motif is highly anisotropic, and that this anisotropy results from long-range elastic couplings involving all the duplex base pairs between the crossovers. The duplex stretch modulus decreases due to localized defects, while the twist stiffness is close to that of an isolated duplex. The DX core as a whole follows an analytical beam theory in bending but not in torsion. Our results extend beyond local elastic models of DNA nanostructures and pave the way for probing peculiar mechanical properties of other key motifs for DNA and RNA nanotechnology.

biophysics↗

bioRxiv2025

Sequence-dependent shape and stiffness of DNA and RNA double helices: hexanucleotide scale and beyond

The structure and deformability of double-stranded DNA and RNA depend on the sequence of bases, affecting biological processes and nanostructure design. Despite intense research, the dependence is incompletely understood. Here we present mechanical properties of DNA and RNA duplexes inferred from atomic-resolution, explicit-solvent molecular dynamics (MD) simulations of 107 DNA and 107 RNA oligomers containing all hexanucleotide sequences. The sequence-specific parameters include structure and stiffness at the rigid base level, the width and stiffness of major and minor grooves, and global material constants such as stretch modulus, twist rigidity, or bending and twisting persistence lengths. We propose a simple model to predict sequence-dependent shape and harmonic stiffness for arbitrary sequence, validate it on an independent set of MD simulations for DNA and RNA duplexes containing all pentamers, and demonstrate its utility in various applications. The large amount of simulated data enabled us to study rare events, such as base-pair opening lifetimes, or flips of the RNA sugar pucker into the B domain and the related dynamics of the 2-OH group. Together, this work provides a comprehensive sequence-specific description of DNA and RNA duplex mechanics, forming a baseline for further research and allowing for a broad range of applications.

biophysics↗

bioRxiv2023

Temperature-dependent twist of double-stranded RNA probed by magnetic tweezers experiments and molecular dynamics simulations

RNA plays critical roles in the transmission and regulation of genetic information and is increasingly used in biomedical and biotechnological applications. Functional RNAs contain extended double-stranded regions and the structure of double-stranded RNA (dsRNA) has been revealed at high-resolution. However, the dependence of the properties of the RNA double helix on environmental effects, notably temperature, is still poorly understood. Here, we use single-molecule magnetic tweezers measurements to determine the dependence of the dsRNA twist on temperature. We find that dsRNA unwinds with increasing temperature, even more than DNA, with {Delta}TwRNA = -14.4 {+/-} 0.7 {o}/({degrees}C{middle dot}kbp), compared to {Delta}TwDNA = -11.0 {+/-} 1.2 {o}/({degrees}C{middle dot}kbp). All-atom molecular dynamics (MD) simulations using a range of nucleic acid force fields, ion parameters, and water models correctly predict that dsRNA unwinds with rising temperature, but significantly underestimate the magnitude of the effect. These MD data, together with additional MD simulations involving DNA and DNA-RNA hybrid duplexes, reveal a linear correlation between twist temperature decrease and the helical rise, in line with DNA but at variance with RNA experimental data. We speculate that this discrepancy might be caused by some unknown bias in the RNA force fields tested, or by as yet undiscovered transient alternative structures in the RNA duplex. Our results provide a baseline to model more complex RNA assemblies and to test and develop new parameterizations for RNA simulations. They may also inspire physical models of temperature-dependent dsRNA structure.

biophysics↗

bioRxiv2023

Mechanical Properties of DNA Double-Crossover Motif

The double-crossover (DX) motif is a key building block of DNA nanostructures. It connects two double helices by two closely spaced Holliday junctions. Despite its prominent importance, the structure and elasticity of the DX motif is not fully understood. Here we employ extensive all-atom molecular dynamics (MD) simulations of an antiparallel DNA DX motif with two full turns between crossovers to infer its global structure and deformability. We quantitatively reproduce the experimentally known two-fold increase of bending stiffness upon incorporation of a DNA duplex into the DX motif, and find out that its stretching and twisting stiffness are only slightly influenced. To further describe the motif, we define four effective rigid bodies, each involving several base pairs flanking the Holliday junctions from the outside, and consider internal coordinates capturing relative displacement and orientation of the bodies. Time series of the coordinates from MD then yield the global structure of the DX motif and its stiffness in the harmonic approximation.

biophysics↗

bioRxiv2020

Impact of the nucleosome histone core on the structure and dynamics of DNA containing pyrimidine-pyrimidone (6-4) photoproduct

The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion, which constitutes a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with compaction proteins, and notably histones, affects the mechanism of its mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA containing 64-PP lesions within the nucleosome core particle by atomic-resolution molecular dynamics simulations at the multi-microsecond time scale. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, we also show that local DNA flexibility at the damaged site is enhanced, due to imperfect structural adaptation to restraints imposed by the histone core. In particular, if 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails.

biophysics↗