42 research outputs found
Molecular velocity auto-correlation of simple liquids observed by NMR MGSE method
The velocity auto-correlation spectra of simple liquids obtained by the NMR
method of modulated gradient spin echo show features in the low frequency range
up to a few kHz, which can be explained reasonably well by a long
time tail decay only for non-polar liquid toluene, while the spectra of polar
liquids, such as ethanol, water and glycerol, are more congruent with the model
of diffusion of particles temporarily trapped in potential wells created by
their neighbors. As the method provides the spectrum averaged over ensemble of
particle trajectories, the initial non-exponential decay of spin echoes is
attributed to a spatial heterogeneity of molecular motion in a bulk of liquid,
reflected in distribution of the echo decays for short trajectories. While at
longer time intervals, and thus with longer trajectories, heterogeneity is
averaged out, giving rise to a spectrum which is explained as a combination of
molecular self-diffusion and eddy diffusion within the vortexes of hydrodynamic
fluctuations.Comment: 8 pages, 6 figur
Heat and charge transport in H2O at ice-giant conditions from ab initio molecular dynamics simulations
The impact of the inner structure and thermal history of planets on their observable features, such as luminosity or magnetic field, crucially depends on the poorly known heat and charge transport properties of their internal layers. The thermal and electric conductivities of different phases of water (liquid, solid, and super-ionic) occurring in the interior of ice giant planets, such as Uranus or Neptune, are evaluated from equilibrium ab initio molecular dynamics, leveraging recent progresses in the theory and data analysis of transport in extended systems. The implications of our findings on the evolution models of the ice giants are briefly discussed
On the Binding Free Energy and Molecular Origin of Sickle Cell Hemoglobin Aggregation
International audienceProtein aggregation is associated with various diseases, including Alzheimer and Parkinson as well as sickle cell disease (SCD). From a molecular point of view, protein aggregation depends on a complex balance of electrostatic and hydrophobic interactions mediated by water. An impressive manifestation of the importance of this balance concerns the human hemoglobin (HbA) mutant, HbS (sickle cell Hb), where a single substitution at the 6th position of HbA β-chains, from glutamic acid to valine, causes the polymerization of deoxygenated HbS (deoxy-HbS), responsible for SCD. HbS polymerization is believed to occur via a double nucleation mechanism initiated by the formation of HbS fibers (homogeneous nucleation), followed by fiber growth. Furthermore, it was proposed that homogeneous nucleation proceeds through a two-step mechanism, where metastable dense clusters play the role of nucleation precursors. Thus, hindering or delaying the formation of such precursors could represent a potential SCD therapeutic route. Here, we study, through molecular dynamics, the binding free energy and protein–protein contacts involved in the deoxy-HbS dimer aggregation and stabilization process. A binding free energy of ∼−14.0 ± 1 kcal/mol is estimated from a one-dimensional potential of mean force. Analysis of protein–protein interactions shows that both electrostatic and van der Waals interactions play an important role on the aggregation of HbS. With respect to the former, our results indicate that aggregation is largely favored by the formation of salt bridges (SB), mostly, Lys–Glu, Lys–Asp, and Heme-Lys SB, which outweigh electrostatic repulsions involving similar residues. Thus, our results suggest that a potential antisickling drug could be one with the ability to weaken or hinder the formation of a few SB between carboxylate and ammonium groups
The Changing Hydrogen-Bond Network of Water from the Bulk to the Surface of a Cluster: A Born−Oppenheimer Molecular Dynamics Study
Mechanistic Insights into Polyphenols’ Aggregation Inhibition of α‑Synuclein and Related Peptides
While several polyphenols were found to either inhibit
or modulate
the aggregation of proteins implicated in neurodegenerative diseases,
such as Parkinson’s disease (PD), discrepant action mechanisms
have been reported. This, in addition to some polyphenols’
pan-assay interference compounds’ reputation, casts some doubts
concerning their therapeutic relevance. Here, we studied, through
molecular dynamics and enhanced sampling methods, the aggregation
of 11-mer peptides from the non-amyloid-β component, an aggregation-prone
domain of α-synuclein (α-syn) implicated in PD and other
synucleinopathies, in neat water and aqueous solutions of resveratrol
(RSV) and gallic acid (GA). Further, simulations of the complete protein
were carried out in aqueous urea, RSV, and GA solutions. Our results
show that peptide aggregation is not disrupted by either phenolic
compound. Thus, instead, intrusion of RSV and GA in the inter-peptide
region induces a peptide–peptide re-orientation, favoring terminal
interactions that manifest in the formation of barrierless solvent-separated
configurations. Moreover, although the (poly)phenols induce a pronounced
peptide dewetting at high concentrations, β-sheet-rich regions,
a hallmark of α-syn aggregation, are not disrupted. Thus, our
results indicate that, if anything, RSV and GA delay or modulate peptide
aggregation at high concentrations via the stabilization of solvent-separated
conformations as opposed to aggregation inhibition. Structural analysis
of the full protein, however, shows that the (poly)phenols induce
more extended conformations of α-syn, similar to urea, possibly
also influencing its aggregation propensity. However, opposite to
urea, the (poly)phenols reduce α-syn’s conformational
space, likely due to steric effects and a slowdown of the solvent
dynamics. These effects are concentration-dependent and possibly unattainable
at therapeutic-relevant concentrations. These results suggest that
the aggregation inhibition activity of RSV and GA in vitro should
involve, instead, either the non-covalent binding to oligomeric intermediates
or the stabilization of the monomer and/or oligomers through the formation
of covalent bonds of the respective quinones with α-syn. In
addition, the enhanced aggregation tendency of the peptides observed
here could be associated with the formation of non-toxic oligomers,
reported for some polyphenols
Translational and rotational dynamics of high and low density TIP4P/2005 water
We use molecular dynamics simulations using TIP4P/2005 to investigate the self- and distinct-van Hove functions for different local environments of water, classified using the local structure index as an order parameter. The orientational dynamics were studied through the calculation of the time-correlation functions of different-order Legendre polynomials in the OH-bond unit vector. We found that the translational and orientational dynamics are slower for molecules in a low-density local environment and correspondingly the mobility is enhanced upon increasing the local density, consistent with some previous works, but opposite to a recent study on the van Hove function. From the analysis of the distinct dynamics, we find that the second and fourth peaks of the radial distribution function, previously identified as low density-like arrangements, show long persistence in time. The analysis of the time-dependent interparticle distance between the central molecule and the first coordination shell shows that particle identity persists longer than distinct van Hove correlations. The motion of two first-nearest-neighbor molecules thus remains coupled even when this correlation function has been completely decayed. With respect to the orientational dynamics, we show that correlation functions of molecules in a low-density environment decay exponentially, while molecules in a local high-density environment exhibit bi-exponential decay, indicating that dynamic heterogeneity of water is associated with the heterogeneity among high-density and between high-density and low-density species. This bi-exponential behavior is associated with the existence of interstitial waters and the collapse of the second coordination sphere in high-density arrangements, but not with H-bond strength
Conflicting Interpretations of Scientific Pedagogy
Not surprisingly historical studies have suggested that there is a distance between concepts of teaching methods, their interpretations and their actual use in the classroom. This issue, however, is not always pitched to the personal level in historical studies, which may provide an alternative insight on how teachers conceptualise and engage with concepts of teaching methods. This article provides a case study on this level of conceptualisation by telling the story of Rómulo de Carvalho, an educator from mid-twentieth century Portugal, who for over 40 years engaged with the heuristic and Socratic methods. The overall argument is that concepts of teaching methods are open to different interpretations and are conceptualised within the melting pot of external social pressures and personal teaching preferences. The practice and thoughts of Carvalho about teaching methods are scrutinised to unveil his conflicting stances: Carvalho was a man able to question the tenets of heurism, but who publicly praised the heurism-like “discovery learning” method years later. The first part of the article contextualises the arrival of heurism in Portugal and how Carvalho attacked its philosophical tenets. In the second part, it dwells on his conflicting positions in relation to pupil-centred approaches. The article concludes with an appreciation of the embedded conflicting nature of the appropriation of concepts of teaching methods, and of Carvalho’s contribution to the development of the philosophy of practical work in school science