Dynamical Rearrangements Research Articles

TimeSOAP: Tracking high-dimensional fluctuations in complex molecular systems via time variations of SOAP spectra.

Many molecular systems and physical phenomena are controlled by local fluctuations and microscopic dynamical rearrangements of the constitutive interacting units that are often difficult to detect. This is the case, for example, of phase transitions, phase equilibria, nucleation events, and defect propagation, to mention a few. A detailed comprehension of local atomic environments and of their dynamic rearrangements is essential to understand such phenomena and also to draw structure-property relationships useful to unveil how to control complex molecular systems. Considerable progress in the development of advanced structural descriptors [e.g., Smooth Overlap of Atomic Position (SOAP), etc.] has certainly enhanced the representation of atomic-scale simulations data. However, despite such efforts, local dynamic environment rearrangements still remain difficult to elucidate. Here, exploiting the structurally rich description of atomic environments of SOAP and building on the concept of time-dependent local variations, we developed a SOAP-based descriptor, TimeSOAP (τSOAP), which essentially tracks time variations in local SOAP environments surrounding each molecule (i.e., each SOAP center) along ensemble trajectories. We demonstrate how analysis of the time-series τSOAP data and of their time derivatives allows us to detect dynamic domains and track instantaneous changes of local atomic arrangements (i.e., local fluctuations) in a variety of molecular systems. The approach is simple and general, and we expect that it will help shed light on a variety of complex dynamical phenomena.

BOTAN: BOnd TArgeting Network for prediction of slow glassy dynamics by machine learning relative motion.

Recent developments in machine learning have enabled accurate predictions of the dynamics of slow structural relaxation in glass-forming systems. However, existing machine learning models for these tasks are mostly designed such that they learn a single dynamic quantity and relate it to the structural features of glassy liquids. In this study, we propose a graph neural network model, "BOnd TArgeting Network," that learns relative motion between neighboring pairs of particles, in addition to the self-motion of particles. By relating the structural features to these two different dynamical variables, the model autonomously acquires the ability to discern how the self motion of particles undergoing slow relaxation is affected by different dynamical processes, strain fluctuations and particle rearrangements, and thus can predict with high precision how slow structural relaxation develops in space and time.

Fragility in glassy liquids: A structural approach based on machine learning.

The rapid rise of viscosity or relaxation time upon supercooling is a universal hallmark of glassy liquids. The temperature dependence of viscosity, however, is quite nonuniversal for glassy liquids and is characterized by the system's "fragility," with liquids with nearly Arrhenius temperature-dependent relaxation times referred to as strong liquids and those with super-Arrhenius behavior referred to as fragile liquids. What makes some liquids strong and others fragile is still not well understood. Here, we explore this question in a family of harmonic spheres that range from extremely strong to extremely fragile, using "softness," a structural order parameter identified by machine learning to be highly correlated with dynamical rearrangements. We use a support vector machine to identify softness as the same linear combination of structural quantities across the entire family of liquids studied. We then use softness to identify the factors controlling fragility.

Substrate induced dynamical remodeling of the binding pocket generates GTPase specificity in DOCK family of guanine nucleotide exchange factors

Dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) activate two members of Rho family GTPases, Rac1/Cdc42, to exert diverse cellular processes, including cell migration. As DOCK GEFs have been critically implicated in tumour cell migration, understanding their function and specificity is imperative for designing anti-metastatic drugs. Based on their GTPase specificity they have been classified as Rac, Cdc42 and dual specific GEFs. Despite extensive structural studies, the factors that determine GTPase specificity of DOCK GEFs have remained elusive. Here, we show that subtle dynamical coupling between GEF and GTPase structures modulate the binding interface to generate mutual specificity. To cluster the dynamically coupled residues in GEF-GTPase complexes a novel intra-residue backbone-torsion-angles based mutual information (TMI) technique was employed. TMI was calculated from 4500 trajectories obtained from a total of 4.5μs molecular dynamics simulations performed on members of all the three clades of DOCK GEFs. The obtained clusters suggest a specificity generation mechanism that involves optimization of the binding pocket for the crucial divergent residue at the 56th position of Rac/Cdc42 (FCdc42/WRac1). These clusters encompass five residues from the structural segment lobe C - α10 helix of the DOCK proteins and functional SWI region of GTPase, which induce orchestrated structural modulations to generate the specificity. Even the conserved residues from SWI region are seen to augment the specificity defining dynamical rearrangements. Furthermore, the proposed dynamical GTPase- DOCK GEF specificity model was verified using mutagenesis studies on Rac1 and dual GTPase specific Dock2 and Dock6, respectively. Thus the current study provides the generic substrate specificity determinants of DOCK GEFs, which are not apparent from the conventional structural analysis.

Finding defects in disorder: Strain-dependent structural fingerprint of plasticity in granular materials

When subjected to loads, granular materials tend to yield and exhibit some localized particle reorganizations. Due to the complex disordered structure of granular materials, it is challenging to identify the key preexisting defects in the static, unloaded structure that eventually promotes dynamical particle rearrangements once a load is applied. Here, based on discrete element simulations of an archetypal frictional granular material model, we introduce a machine learning framework that pinpoints such structural defects with unprecedented accuracy. We show that the optimal structural fingerprint of plastic flow defects depends on strain, wherein the plastic flow is governed by short-range defects at low strain but become dominated by medium-range defects at high strain.

Dynamical Rearrangements of 3-D Vortex Structures in Moving Domain Walls in Continuous and Antidot Patterned Permalloy Films

The motion of a domain wall in a magnetic film with an antidot array leads to the formation of a vortex magnetization reversal zone moving along the sample. A description of the magnetization dynamics in the film is obtained by micromagnetic simulations based on the Landau-Lifshitz-Gilbert equation for various film thickness and hole arrangement and size. We show that the magnetization reversal zone either passes through the antidot array or freezes on it. Using a special technique for visualizing vortex structures, based on the calculation of topological charges of two types, we establish the relationship between the magnetization dynamics and the types of vortex structures.

Jetting to dripping transition: Critical aspect ratio in step emulsifiers

Fully three-dimensional, time-dependent, direct simulations of the non-ideal Navier-Stokes equations for a two-component fluid shed light into the mechanism which inhibits droplet breakup in step emulsifiers below a critical threshold of the width-to-height (w/h) ratio of the microfluidic nozzle. Below w/h ∼ 2.6, the simulations provide evidence of a smooth topological transition of the fluid from the confined rectangular channel geometry to an isotropic (spherical) expansion of the fluid downstream the nozzle step. Above such threshold, the transition from the inner to the outer space involves a series of dynamical rearrangements which keep the free surface in mechanical balance. Such rearrangements also induce a backflow of the ambient fluid which, in turn, leads to jet pinching and ultimately to its rupture, namely, droplet formation. The simulations show remarkable agreement with the experimental value of the threshold, which is found around w/h ∼ 2.56.

Electronic Structure Rearrangements in Hybrid Ribozyme/Protein Catalysis

We analyzed the electronic structural changes that occur in the reaction cycle of a biological catalyst composed of RNA and protein, and elucidated the dynamical rearrangements of the electronic structure that was obtained from our previous study in which ab initio quantum mechanics/molecular mechanics molecular dynamics simulations were performed. Notable results that we obtained include the generation of a reactive HOMO that is responsible for bond formation in the initial stages of the reaction, and the appearance of a reactive LUMO that is involved in the bond rupture that leads to products. We denote these changes as dynamical induction of the reactive HOMO (DIRH) and LUMO (DIRL), respectively. Interestingly, we also find that the induction of the reactive HOMO is enhanced by the formation of a low-barrier hydrogen bond (LBHB), which, to the best of our knowledge, represents a novel role for LBHBs in enzymatic systems.

Relationship between local structure and relaxation in out-of-equilibrium glassy systems

The dynamical glass transition is typically taken to be the temperature at which a glassy liquid is no longer able to equilibrate on experimental timescales. Consequently, the physical properties of these systems just above or below the dynamical glass transition, such as viscosity, can change by many orders of magnitude over long periods of time following external perturbation. During this progress toward equilibrium, glassy systems exhibit a history dependence that has complicated their study. In previous work, we bridged the gap between structure and dynamics in glassy liquids above their dynamical glass transition temperatures by introducing a scalar field called "softness," a quantity obtained using machine-learning methods. Softness is designed to capture the hidden patterns in relative particle positions that correlate strongly with dynamical rearrangements of particle positions. Here we show that the out-of-equilibrium behavior of a model glass-forming system can be understood in terms of softness. To do this we first demonstrate that the evolution of behavior following a temperature quench is a primarily structural phenomenon: The structure changes considerably, but the relationship between structure and dynamics remains invariant. We then show that the relaxation time can be robustly computed from structure as quantified by softness, with the same relation holding both in equilibrium and as the system ages. Together, these results show that the history dependence of the relaxation time in glasses requires knowledge only of the softness in addition to the usual state variables.

Structure in sheared supercooled liquids: Dynamical rearrangements of an effective system of icosahedra.

We consider a binary Lennard-Jones glassformer whose super-Arrhenius dynamics are correlated with the formation of particles organized into icosahedra under simple steady state shear. We recast this glassformer as an effective system of icosahedra [Pinney et al., J. Chem. Phys. 143, 244507 (2015)]. From the observed population of icosahedra in each steady state, we obtain an effective temperature which is linearly dependent on the shear rate in the range considered. Upon shear banding, the system separates into a region of high shear rate and a region of low shear rate. The effective temperatures obtained in each case show that the low shear regions correspond to a significantly lower temperature than the high shear regions. Taking a weighted average of the effective temperature of these regions (weight determined by region size) yields an estimate of the effective temperature which compares well with an effective temperature based on the global mesocluster population of the whole system.

Investigating the Handedness Dynamics of Tetrasomes

Nucleosomes formed by DNA wrapping around histone octamers are the basic compaction unit of eukaryotic chromatin. Besides packaging DNA, they also play an essential role in genome regulation by controlling DNA accessibility. Their assembly follows a precise pathway in which first tetramers of H3 and H4 histones bind to DNA, forming tetrasomes, and then two dimers of H2A and H2B histones complete the formation of full nucleosomes. Here, we present our single-molecule studies on the assembly of tetrasomes by directly measuring the length, twist, and torque of single DNA molecules using Freely Orbiting Magnetic Tweezers (FOMT) and electro-Magnetic Torque Tweezers (eMTT). By this means, we have investigated both the replication-coupled histone H3.1 and its replication-independent variant histone H3.3. Our results indicate that tetrasomes exhibit a spontaneous flipping between a preferentially occupied left-handed state (ΔLk = −0.73) and a less populated right-handed state (ΔLk = +1.0), while weak torques convert them from one state into the other. In addition, the stepwise assembly of full nucleosomes suggests that tetrasomes undergoing changes in handedness remain viable intermediates. We further show how studies performed on tetrasomes that are artificially modified at their H3-H3 interface provide more insight into their handedness dynamics. Our findings reveal dynamical rearrangements of the nucleosomal structure that illustrate how chromatin could regulate DNA-supercoiling.

Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels.

Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insight into the transition steps, which are difficult to access experimentally. In this study, we use MD simulations on wild type KirBac1.1 and an activatory mutant to investigate activation gating of KirBac channels. Full atomistic MD simulations revealed that introducing glutamate in position 143 causes significant widening at the helix bundle crossing gate, enabling water flux into the cavity. Further, global rearrangements including a twisting motion as well as local rearrangements at the subunit interface in the cytoplasmic domain were observed. These structural rearrangements are similar to recently reported KirBac3.1 crystal structures in closed and open conformation, suggesting that our simulations capture major conformational changes during KirBac1.1 opening. In addition, an important role of protein–lipid interactions during gating was observed. Slide-helix and C-linker interactions with lipids were strengthened during activation gating.

Nucleosome Assembly Dynamics Involve Spontaneous Fluctuations in the Handedness of Tetrasomes

DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length of single DNA molecules, we monitor the real-time loading of tetramers or complete histone octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1). Remarkably, we find that tetrasomes exhibit spontaneous flipping between a preferentially occupied left-handed state (ΔLk = -0.73) and a right-handed state (ΔLk = +1.0), separated by a free energy difference of 2.3 kBT (1.5 kcal/mol). This flipping occurs without concomitant changes in DNA end-to-end length. The application of weak positive torque converts left-handed tetrasomes into right-handed tetrasomes, whereas nucleosomes display more gradual conformational changes. Our findings reveal unexpected dynamical rearrangements of the nucleosomal structure, suggesting that chromatin can serve as a "twist reservoir," offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.

Nucleosome Assembly Dynamics Involve Spontaneous Fluctuations in the Handedness of Tetrasomes

Nucleosomes play crucial roles in eukaryotic cells as they form the basic compaction unit of DNA, and impact the accessibility of the DNA for transcription and replication. How the assembly, stability, and disassembly of nucleosomes affect the interplay between compaction and accessibility forms a question of key interest. Here we use freely-orbiting magnetic tweezers (FOMT), which can measure in real time the changes in length and twist of individually tethered DNA molecules. We monitor how Nucleosome Assembly Protein-1 (NAP1) loads either histone tetramers (an important intermediate in dis/assembly or remodeling) or complete histone octamers onto DNA, thus forming nucleosomes. Remarkably, tetrasomes are observed to exhibit a spontaneous flipping between DNA states with linking number ΔLk=-0.73 and ΔLk=+1.0, without concomitant changes in DNA end-to-end length. Such behavior is absent in the case of nucleosomes. The statistics of tetrasome flipping shows that the preferentially occupied left-handed state has a probability p=0.9. The difference in free energy between these two states is thus 2.3kBT. We also demonstrate how controlled application of positive torque can drive tetrasome occupancy from left-handed to right-handed states. To exclude effects of the assembly protein NAP1, we repeated these experiments with tetrasomes assembled in the conventional way using salt dialysis. These results show that the spontaneous fluctuations in the handedness of tetrasomes are not NAP1 induced. Since we expect the H3-H3 interface to play an important role in the handedness fluctuations, we also studied tetrasomes in which the replication-coupled canonical histone H3 was replaced by the replication-independent variant H3.3, which show very similar behavior. Our findings thus reveal unexpected dynamical rearrangements of the nucleosomal structure that suggest that chromatin can serve as a ‘twist reservoir’, offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.

Quantum effects of hydrogen nuclei on a structure and a dynamical rearrangement of hydrogen-bond networks

To understand anomalous energetics and dynamics in water, nuclear quantum effects such as zero-point energy and delocalization of wave packets (WPs) representing water hydrogen atoms should be essential. However, since quantum calculations of many-body dynamics are highly complicated in general, none has yet directly viewed the quantum WP dynamics of hydrogen atoms in liquid water. Our semiquantum molecular dynamics simulation for the first time made it possible to observe the hydrogen WP dynamics in liquid water. Here, we demonstrate that the microscopic WP dynamics are closely correlated to and play key roles in the dynamical rearrangements in the hydrogen-bond network (HBN) of liquid water. Especially, the memory loss of the dipolar angle formed by two waters is accelerated with the nuclear quantum effect introduced by the nuclear WP, rationalizing the faster memory decay of the HBN in the quantum liquid water. We found the quantum effects of hydrogen atoms on mesoscopic liquid water behaviors such as intermittent collective motions associated with the rearrangement of HBN and the concomitant fluctuation and relaxation. Our results will provide new physical insights on HBN dynamics in water whose significance is not limited to the pure liquid dynamics but also for understanding chemical and biological reactions in liquid water.

MD Simulations of KirBac1.1 Mutants Reveal Gating Changes at the Bundle Crossing Region

Inwardly rectifying potassium (Kir) channels play important physiological roles in a variety of cells including heart rate, insulin secretion or fluid balance. Their importance is further illustrated by the fact that inherited mutations are linked to diseases including Andersen Tawil Syndrome, Bartter syndrome or neonatal diabetes. Their activity is controlled by dynamical conformational changes that regulate ion flow through the central pore of Kir channels. Understanding the dynamical rearrangements of Kir channels during activation gating requires not only high-resolution structure information from channels crystallized in different conformations but insight into the transition steps. Guided by mutations that are known to increase channel activity (1), molecular dynamics simulations of the WT KirBac1.1 crystal structure and the G143E mutant have been performed. Full atomistic MD simulations revealed that introducing a glutamate in position 143 causes significant widening of the pore. In all our simulations the bundle crossing opened to 17 A compared to the WT. Comparison of the mutant KirBac1.1 with the open structure of KirBac3.1 reveals that the pore radius reaches identical values. Furthermore the global rearrangements including a rotation and a bending of the lower part of TM2 are identical in both structures, suggesting that the final structure of the G143E mutant after 60 ns represents an open conformation. Simulations further revealed that deprotonation is essential for channel opening. This is further supported by investigations with non-charged amino acids in this position, which do not lead to channel opening on the nanosecond time scale.(1) Paynter, J. J., Andres-Enguix, I., Fowler, P. W., Tottey, S., Cheng, W., Enkvetchakul, D., Bavro, V. N., Kusakabe, Y., Sansom, M. S. P., Robinson, N. J., Nichols, C. G., and Tucker, S. J. (2010) J. Biol. Chem 285, 40754-40761.

Group-size distribution of skeins of wild geese

In appropriate situations, large populations of geese exhibit dynamical rearrangements by repeated mergers and splits among the groups. We describe the grouping process in terms of a mean-field model based on the Smoluchowski equation of coagulation with fragmentation and observationally plausible kernels. To verify our model, we conducted field observations on skeins of airborne geese, noting both the group-size distribution and the group-forming processes. We found that the group-size distribution we obtained in our field measurements could be represented by a fractional power function with an exponential cutoff. This function matches the asymptotic form of the steady-state solution of our model. Furthermore, we estimated the effective number of individuals involved in interactions by comparison of the model to our field data.

Microscopic sub-barrier fusion calculations for the neutron star crust

Fusion of very neutron-rich nuclei may be important to determine the composition and heating of the crust of accreting neutron stars. Fusion cross sections are calculated using time-dependent Hartree-Fock theory coupled with density-constrained Hartree-Fock calculations to deduce an effective potential. Systems studied include ${}^{16}$O+${}^{16}$O, ${}^{16}$O+${}^{24}$O, ${}^{24}$O+${}^{24}$O, ${}^{12}$C+${}^{16}$O, and ${}^{12}$C+${}^{24}$O. We find remarkable agreement with experimental cross sections for the fusion of stable nuclei. Our simulations use the SLy4 Skyrme force that has been previously fit to the properties of stable nuclei, and no parameters have been fit to fusion data. We compare our results to the simple S\~ao Paulo static barrier penetration model. For the asymmetric systems ${}^{12}$C+${}^{24}$O or ${}^{16}$O+${}^{24}$O we predict an order of magnitude larger cross section than those predicted by the S\~ao Paulo model. This is likely due to the transfer of neutrons from the very neutron rich nucleus to the stable nucleus and dynamical rearrangements of the nuclear densities during the collision process. These effects are not included in potential models. This enhancement of fusion cross sections, for very neutron rich nuclei, can be tested in the laboratory with radioactive beams.

Broadband Depolarized Light Scattering Study of Diluted Protein Aqueous Solutions

A broadband depolarized light scattering (DLS) study is performed on diluted lysozyme aqueous solutions as a function of temperature and concentration. The dynamical susceptibility, obtained in a wide spectral range (0.6-36000 GHz) through the coupled use of interferometric and dispersive devices, is interpreted and compared with neutron scattering and Raman-induced optical Kerr-effect literature data, thus giving a general picture of relaxation phenomena. We show that the proposed approach represents a suitable tool for investigating the hydration dynamics of protein-water solutions. A detailed analysis of the quasi-elastic scattering region evidences the existence of two distinct relaxational processes at picosecond time scales. The fast process (fractions of picosecond) is attributed to bulk water dynamics, while the slow one (few picoseconds) is attributed to dynamical rearrangements of water molecules strongly influenced by the protein (hydration water). The retardation effect here estimated of about 6-7 can be regarded as a direct measure of the increased protein-water and water-water hydrogen bond stability of the water molecules within the protein hydration shell. Interestingly, a similar effect was previously observed on small hydrophilic sugar molecules. Moreover, backbone and side chains torsional motions of the protein in the 600-5300 GHz frequency range are found to be insensitive to thermal variations and to eventual changes occurring in the premelting zone.

Dynamics of electron distributions probed by helium scattering

Helium atom scattering (HAS) is the most important tool for surface science investigations.The analysis of helium scattering off a solid surface allows for a detailed analysis of itsstructural and dynamical properties. In this work we show how the dynamicsof electron distributions at a metal surface can be investigated by HAS in theadiabatic approximation. First we examine the anticorrugating effect, namelythe property of the He–surface potential of those metal systems in which theclassical turning points of He beams are farther away from the surface layer at thebridge than at top sites. Anticorrugation for the system He/Cu(111) is examinedin detail by a density functional theory (DFT) calculation and compared withthe corrugating behaviour of He/Al(111). To explain such an effect the chargepolarization of the system is crucial. Second we consider theoretically a surprisingrestricted diffusion result in the normal direction for Na adatoms on Cu(001) atcoverages larger than 0.04 ML, obtained by measurements with spin polarized 3He beams. From DFT calculations for this system a model for the description of the He–surfaceinteraction based on the effective medium theory, which accounts for the observedphenomenon, is discussed. We show that the surface charge distribution probed by HAS isaltered by the local concentration of the diffusing adatoms which is fluctuating with timeand producing variations in the apparent height of the adatom measured by HAS. Ourcalculations demonstrate that such electronic dynamical rearrangements can be probed by the 3He spin echo technique, which could be extended to other studies of surface electronicproperties.