Hindered intermolecular stacking of anti-parallel telomeric G-quadruplexes.

Telomeric G-quadruplexes (G4s) are non-canonical DNA structures composed of TTAGGG repeats. They are extensively studied both as biomolecules key for genome stability and as promising building blocks and functional elements in synthetic biology and nanotechnology. This is why it is extremely important to understand how the interaction between G4s is affected by their topology.

Water slowing down drives the occurrence of the low temperature dynamical transition in microgels.

The protein dynamical transition marks an increase in atomic mobility and the onset of anharmonic motions at a critical temperature ( ), which is considered relevant for protein functionality. This phenomenon is ubiquitous, regardless of protein composition, structure and biological function and typically occurs at large protein content, to avoid water crystallization. Recently, a dynamical transition has also been reported in non-biological macromolecules, such as poly(-isopropyl acrylamide) (PNIPAM) microgels, bearing many similarities to proteins.

Stacking Interactions and Flexibility of Human Telomeric Multimers.

G-quadruplexes (G4s) are helical four-stranded structures forming from guanine-rich nucleic acid sequences, which are thought to play a role in cancer development and malignant transformation. Most current studies focus on G4 monomers, yet under suitable and biologically relevant conditions, G4s undergo multimerization. Here, we investigate the stacking interactions and structural features of telomeric G4 multimers by means of a novel low-resolution structural approach that combines small-angle X-ray scattering (SAXS) with extremely coarse-grained (ECG) simulations.

Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir.

The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site.

Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes.

Telomeric G-quadruplexes (G4s) are promising targets in the design and development of anticancer drugs. Their actual topology depends on several factors, resulting in structural polymorphism. In this study, we investigate how the fast dynamics of the telomeric sequence AG3(TTAG3)3 (Tel22) depends on the conformation.

Role of fast dynamics in the complexation of G-quadruplexes with small molecules.

G-quadruplexes (G4s) formed by the human telomeric sequence AG (TTAG) (Tel22) play a key role in cancer and aging. We combined elastic incoherent neutron scattering (EINS) and quasielastic incoherent neutron scattering (QENS) to characterize the internal dynamics of Tel22 G4s and to assess how it is affected by complexation with two standard ligands, Berberine and BRACO19. We show that the interaction with the two ligands induces an increase of the overall mobility of Tel22 as quantified by the mean squared displacements (MSD) of hydrogen atoms.

Solid wetting-layers in inorganic nano-reactors: the water in imogolite nanotube case.

By combined use of wide-angle X-ray scattering, thermo-gravimetric analysis, inelastic neutron scattering, density functional theory and density functional theory molecular dynamics simulations, we investigate the structure, dynamics and stability of the water wetting-layer in single-walled aluminogermanate imogolite nanotubes (SW Ge-INTs): an archetypal system for synthetically controllable and monodisperse nano-reactors. We demonstrate that the water wetting-layer is strongly bound and solid-like up to 300 K under atmospheric pressure, with dynamics markedly different from that of bulk water. Atomic-scale characterisation of the wetting-layer reveals organisation of the HO molecules in a curved triangular sublattice stabilised by the formation of three H-bonds to the nanotube's inner surface, with covalent interactions sufficiently strong to promote energetically favourable decoupling of the HO molecules in the adlayer.

Water-Polymer Coupling Induces a Dynamical Transition in Microgels.

The long debated protein dynamical transition was recently found also in nonbiological macromolecules, such as poly- N-isopropylacrylamide (PNIPAM) microgels. Here, by using atomistic molecular dynamics simulations, we report a description of the molecular origin of the dynamical transition in these systems. We show that PNIPAM and water dynamics below the dynamical transition temperature T are dominated by methyl group rotations and hydrogen bonding, respectively.

Evidence of a low-temperature dynamical transition in concentrated microgels.

A low-temperature dynamical transition has been reported in several proteins. We provide the first observation of a "protein-like" dynamical transition in nonbiological aqueous environments. To this aim, we exploit the popular colloidal system of poly--isopropylacrylamide (PNIPAM) microgels, extending their investigation to unprecedentedly high concentrations.

Moving in the Right Direction: Protein Vibrations Steering Function.

Nearly all protein functions require structural change, such as enzymes clamping onto substrates, and ion channels opening and closing. These motions are a target for possible new therapies; however, the control mechanisms are under debate. Calculations have indicated protein vibrations enable structural change.

Hydrogen self-dynamics in liquid H(2)-D(2) mixtures studied through inelastic neutron scattering.

We have measured the dynamic structure factor of liquid para-hydrogen mixed with normal deuterium (T=20 K) at two different concentration levels using incoherent inelastic neutron scattering. This choice has been made since the presence of D(2} modifies the self-dynamics of H(2) in a highly nontrivial way, acting both on its pseudophononic and its diffusive parts in a tunable way. After an accurate data reduction, recorded neutron spectra were studied through the modified Young and Koppel model and the H(2) center-of-mass self-dynamics structure factor was finally extracted for the two mixtures.

Translational diffusion of hydration water correlates with functional motions in folded and intrinsically disordered proteins.

Hydration water is the natural matrix of biological macromolecules and is essential for their activity in cells. The coupling between water and protein dynamics has been intensively studied, yet it remains controversial. Here we combine protein perdeuteration, neutron scattering and molecular dynamics simulations to explore the nature of hydration water motions at temperatures between 200 and 300 K, across the so-called protein dynamical transition, in the intrinsically disordered human protein tau and the globular maltose binding protein.

X-ray scattering determination of the structure of water during carbon nanotube filling.

We present in situ monitoring of water filling of single-walled carbon nanotubes at room temperature, using X-ray scattering. A systematic method is developed to determine the water radial density profile. Water filling is homogeneous below about 5% in mass, whereas it structures into three layers above.

Glassy character of DNA hydration water.

The coherent excitations of DNA hydration water at 100 K have been investigated by neutron scattering spectroscopy to extract the excess signal of D(2)O-hydrated DNA with respect to dry DNA samples. A structural characterization of the sample, through the analysis of the static structure factor, has suggested that DNA hydration water is largely in an amorphous state up to high hydration degree, with only a small contribution coming from slightly deformed crystalline ice. To describe the inelastic spectra of DNA hydration water, we exploited a phenomenological model already applied in similar disordered systems, such as bulk water (Sacchetti et al.

Vibrational collective dynamics of dry proteins in the terahertz region.

The coherent density fluctuations of a perdeuterated dry protein have been studied by Brillouin neutron spectroscopy. Besides a nearly wavevector-independent branch located around 5 meV, a propagating mode with a linear trend at low wavevector Q is revealed. The corresponding speed of 3780 ± 130 m/s is definitely higher than that of hydrated proteins.

Collective density fluctuations of DNA hydration water in the time-window below 1 ps.

The coherent density fluctuations propagating through DNA hydration water were studied by neutron scattering spectroscopy. Two collective modes were found to be sustained by the aqueous solvent: a propagating excitation, characterised by a speed of about 3500 m/s, and another one placed at about 6 meV. These results globally agree with those previously found for the coherent excitations in bulk water, although in DNA hydration water the speed of propagating modes is definitely higher than that of the pure solvent.

Interplay between microscopic diffusion and local structure of liquid water.

We present a quasielastic neutron scattering (QENS) study of single-particle dynamics in pure water, measured at temperatures between 256 and 293 K along an isobaric path at 200 MPa. A thorough analysis of the spectral line shapes reveals a departure from simple models of continuous or jump diffusion, with such an effect becoming stronger at lower temperatures. We show that such a diverging trend of dynamical quantities upon cooling closely resembles the divergent (anomalous) compressibility observed in water by small-angle diffraction.

Collective dynamics of protein hydration water by brillouin neutron spectroscopy.

By a detailed experimental study of THz dynamics in the ribonuclease protein, we could detect the propagation of coherent collective density fluctuations within the protein hydration shell. The emerging picture indicates the presence of both a dispersing mode, traveling with a speed greater than 3000 m/s, and a nondispersing one, characterized by an almost constant energy of 6-7 meV. In agreement with molecular dynamics simulations [Phys.