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We report on a joint theoretical and experimental study of the vibrational dynamics of the type-I clathrates A(8)Sn(44)square (2) (A=K, Rb, Cs, and square stands for a vacancy) by high-resolution inelastic neutron scattering experiments combined with low-temperature specific heat measurements (2-300K). Ab initio lattice dynamics calculations were performed on hypothetical vacancy-free A(8)Sn(46) clathrates in order to determine the phonon dispersions and vibrational density of states Z ( omega ). The temperature dependence of the generalized vibrational density of states (GVDOS) was traced from 420K down to 50K, paying particular attention to the low-energy region of the GVDOS spectra. In the Cs and Rb compounds, the inelastic signal at low energies is dominated by several peaks mainly associated with the dynamics of the alkali metal atoms A in the polyhedral cages of the clathrate structure. In contrast, the low-energy spectrum of the K compound features a more pronounced contribution of the weighed modes of the framework Sn atoms. Upon cooling, the A-weighted modes soften regardless of the nature of the alkali element. The shift observed is similar for the three compounds and of small amplitude, suggestive of a dominant quasi-harmonic behavior above 50K. The distinct dynamics of the K atoms in comparison to Cs and Rb is further demonstrated by the analyses of the low-temperature specific heat data, indicating that the low-energy Sn-weighted modes cannot be described by a Debye model with Einstein-like contributions., CNRS-MPG Program

The human myelin protein P2 is a membrane binding protein believed to maintain correct lipid composition and organization in peripheral nerve myelin. Its function is related to its ability to stack membranes, and this function can be enhanced by the P38G mutation, whereby the overall protein structure does not change but the molecular dynamics increase. Mutations in P2 are linked to human peripheral neuropathy. Here, the dynamics of wild-type P2 and the P38G variant were studied using quasielastic neutron scattering on time scales from 10 ps to 1 ns at 300 K. The results suggest that the mutant protein dynamics are increased on both the fastest and the slowest measured time scales, by increasing the dynamics amplitude and/or the portion of atoms participating in the movement.

Excitations in a spin ice behave as magnetic monopoles, and their population and mobility control the dynamics of a spin ice at low temperature. CdEr2X4 is reported to have the Pauling entropy characteristic of a spin ice, but its dynamics are three orders of magnitude faster than the canonical spin ice Dy2Ti2O7. In this Letter we use diffuse neutron scattering to show that both CdEr2X4 and CdEr2X4 support a dipolar spin ice state-the host phase for a Coulomb gas of emergent magnetic monopoles. These Coulomb gases have similar parameters to those in Dy2Ti2O7, i.e., dilute and uncorrelated, and so cannot provide three orders faster dynamics through a larger monopole population alone. We investigate the monopole dynamics using ac susceptometry and neutron spin echo spectroscopy, and verify the crystal electric field Hamiltonian of the Er3+ ions using inelastic neutron scattering. A quantitative calculation of the monopole hopping rate using our Coulomb gas and crystal electric field parameters shows that the fast dynamics in CdEr2X4 (X = Se, S) are primarily due to much faster monopole hopping. Our work suggests that CdEr2X4 offer the possibility to study alternative spin ice ground states and dynamics, with equilibration possible at much lower temperatures than the rare earth pyrochlore examples.

An essential role of enzymes is to catalyze various chemical reactions in the human body and inhibition of the enzymatic activity by small molecules is the mechanism of action of many drugs or tool compounds used to study biological processes. Here, we investigate the effect on the dynamics of the serine protease alpha-chymotrypsin when in complex with two different covalently bound inhibitors using elastic incoherent neutron scattering. The results show that the inhibited enzyme displays enhanced dynamics compared to the free form. The difference was prominent at higher temperatures (240-310 K) and the type of motions that differ include both small amplitude motions, such as hydrogen atom rotations around a methyl group, and large amplitude motions, such as amino acid side chain movements. The measurements were analyzed with multivariate methods in addition to the standard univariate methods, allowing for a more in-depth analysis of the types of motions that differ between the two forms. The binding strength of an inhibitor is linked to the changes in dynamics occurring during the inhibitor-enzyme binding event and thus these results may aid in the deconvolution of this fundamental event and in the design of new inhibitors.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Knowledge of the structure of a protein can be very informative in determining its function, however, a structure alone does not tell the whole story. In the case of large, dynamic multi-protein systems where a coordinated network of interactions and enzymatic functions are involved, structural and biochemical information may be gainfully combined with knowledge of dynamics [1]. One such system is the bacterial replisome, which consists of more than a dozen interacting proteins and is capable of rapid DNA replication. As such, it is a good model system and a ripe target for antibiotic development. We have focussed on an interaction that involves one of the key organisational centres of the Gram-positive bacterial replisome, the DnaB helicase and its loading partner, DnaI, which together form a tight 6:6 complex prior to loading of the hexameric helicase onto DNA, after which DnaI dissociates [2]. We have separately measured the dynamics of DnaI, DnaB and their complex using elastic, quasielastic and inelastic neutron scattering on IN6 at ILL (Grenoble, France). These measurements have established that the molecular fl exibility and diffusive motions are signifi cantly decreased when DnaI and DnaB are complexed, with DnaB having the greatest fl exibility when free. Further to this, complexation results in an increase in structural rigidity with the DnaB-DnaI complex having a signifi cantly higher effective force constant both above and below the temperature of dynamical transition. The vibrational density of states was also extracted, revealing that the DnaI-DnaB complex has less inelastic vibrational modes than DnaB and DnaI below the absolute value of 20 meV.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Knowledge of the structure of a protein can be very informative in determining its function, however, a structure alone does not tell the whole story. In the case of large, dynamic multi-protein systems where a coordinated network of interactions and enzymatic functions are involved, structural and biochemical information may be gainfully combined with knowledge of dynamics [1]. One such system is the bacterial replisome, which consists of more than a dozen interacting proteins and is capable of rapid DNA replication. As such, it is a good model system and a ripe target for antibiotic development. We have focussed on an interaction that involves one of the key organisational centres of the Gram-positive bacterial replisome, the DnaB helicase and its loading partner, DnaI, which together form a tight 6:6 complex prior to loading of the hexameric helicase onto DNA, after which DnaI dissociates [2]. We have separately measured the dynamics of DnaI, DnaB and their complex using elastic, quasielastic and inelastic neutron scattering on IN6 at ILL (Grenoble, France). These measurements have established that the molecular fl exibility and diffusive motions are signifi cantly decreased when DnaI and DnaB are complexed, with DnaB having the greatest fl exibility when free. Further to this, complexation results in an increase in structural rigidity with the DnaB-DnaI complex having a signifi cantly higher effective force constant both above and below the temperature of dynamical transition. The vibrational density of states was also extracted, revealing that the DnaI-DnaB complex has less inelastic vibrational modes than DnaB and DnaI below the absolute value of 20 meV.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Understanding how proteins interact and behave in large dynamic multi-protein complexes is an important area of significance in many human diseases that are associated with faults in their interactions. Increasing understanding of the well characterized bacterial DNA replication machinery (the replisome) will continue to enrich our understanding of other dynamic complexes, including those that carry out human DNA replication. Although replication proteins are not themselves highly conserved between eubacteria and higher organisms, the replication mechanisms generally are. We focussed on pairwise interactions that involve one of the key organizational centres of the bacterial replisome, the DnaI helicase loader and the DnaB helicase. As a first step, we measured the dynamics of the Bacillus sp. helicase loader DnaI and the DnaB helicase separately, using elastic, quasielastic and inelastic neutron scattering at four instrumental resolutions. This provides a basis for future experiments on the DnaI-DnaB complex. The measurement established that internal molecular flexibility and diffusive motions are significantly higher in DnaB helicase compared to those evaluated in DnaI. The structural rigidity was also studied. The analysis revealed that DnaI structural rigidity is larger than that of DnaB. Furthermore, the method allowed the extraction of vibrational density of states, showing that DnaI has more vibrational modes than DnaB.

Changes of molecular dynamics in the α-to-β transition associated with amyloid fibril formation were explored on apo-myoglobin (ApoMb) as a model system. Circular dichroism, neutron and X-ray scattering experiments were performed as a function of temperature on the protein, at different solvent conditions. A significant change in molecular dynamics was observed at the α-to-β transition at about 55 ˚C, indicating a more resilient high temperature β structure phase. A similar effect at approximately the same temperature was observed in holo-myoglobin, associated with partial unfolding and protein aggregation. A study in a wide temperature range between 20 K and 360 K revealed that a dynamical transition at about 200 K for motions in the 50 ps time scale exists also for a hydrated powder of heat-denatured aggregated ApoMb.