Role Of Structural Heterogeneity Research Articles

The role of structural heterogeneity in the homodimerization of transmembrane proteins.

The equilibrium association of transmembrane proteins plays a fundamental role in membrane protein function and cellular signaling. While the study of the equilibrium binding of single pass transmembrane proteins has received significant attention in experiment and simulation, the accurate assessment of equilibrium association constants remains a challenge to experiment and simulation. In experiment, there remain wide variations in association constants derived from experimental studies of the most widely studied transmembrane proteins. In simulation, state-of-the art methods have failed to adequately sample the thermodynamically relevant structures of the dimer state ensembles using coarse-grained models. In addition, all-atom force fields often fail to accurately assess the relative free energies of the dimer and monomer states. Given the importance of this fundamental biophysical process, it is essential to address these shortcomings. In this work, we establish an effective computational protocol for the calculation of equilibrium association constants for transmembrane homodimer formation. A set of transmembrane protein homodimers, used in the parameterization of the MARTINI v3 force field, are simulated using metadynamics, based on three collective variables. The method is found to be accurate and computationally efficient, providing a standard to be used in the future simulation studies using coarse-grained or all-atom models.

Excited-State Proton Transfer from Embedded Photoacids to Silanols on Mesostructured Surfaces: Role of Structural Heterogeneity

Excited-State Proton Transfer from Embedded Photoacids to Silanols on Mesostructured Surfaces: Role of Structural Heterogeneity

Coherent oscillations in balanced neural networks driven by endogenous fluctuations.

We present a detailed analysis of the dynamical regimes observed in a balanced network of identical quadratic integrate-and-fire neurons with sparse connectivity for homogeneous and heterogeneous in-degree distributions. Depending on the parameter values, either an asynchronous regime or periodic oscillations spontaneously emerge. Numerical simulations are compared with a mean-field model based on a self-consistent Fokker-Planck equation (FPE). The FPE reproduces quite well the asynchronous dynamics in the homogeneous case by either assuming a Poissonian or renewal distribution for the incoming spike trains. An exact self-consistent solution for the mean firing rate obtained in the limit of infinite in-degree allows identifying balanced regimes that can be either mean- or fluctuation-driven. A low-dimensional reduction of the FPE in terms of circular cumulants is also considered. Two cumulants suffice to reproduce the transition scenario observed in the network. The emergence of periodic collective oscillations is well captured both in the homogeneous and heterogeneous setups by the mean-field models upon tuning either the connectivity or the input DC current. In the heterogeneous situation, we analyze also the role of structural heterogeneity.

Structural context of the 2015 pair of Nepal earthquakes (Mw 7.8 and Mw 7.3): an analysis based on slip distribution, aftershock growth, and static stress changes

The Great Himalayan earthquakes are believed to originate on the Main Himalayan Thrust, and their ruptures lead to deformation along the Main Frontal Thrust (MFT). The rupture of the April 25, 2015 (Mw 7.8), earthquake was east-directed, with no part relayed to the MFT. The aftershock distribution, coseismic elevation change of similar to 1 m inferred from the InSAR image, and the spatial correspondence of the subtle surface deformations with PT2, a previously mapped out-of-sequence thrust, lead us to explore the role of structural heterogeneities in constraining the rupture progression. We used teleseismic moment inversion of P- and SH-waves, and Coulomb static stress changes to map the slip distribution, and growth of aftershock area, to understand their relation to the thrust systems. Most of the aftershocks were sourced outside the stress shadows (slip > 1.65 m) of the April 25 earthquake. The May 12 (Mw 7.3) earthquake that sourced on a contiguous patch coincides with regions of increased stress change and therefore is the first known post-instrumentation example of a late, distant, and large triggered aftershock associated with any large earthquake in the Nepal Himalaya. The present study relates the slip, aftershock productivity, and triggering of unbroken stress barriers, to potential out-of-sequence thrusts, and suggests the role of stress transfer in generating large/great earthquakes.

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization.

Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media.

Nanostructural scaling effect in fracturing homogeneous solids

The scaling effect (power law dependence of number of newly-formed damages on damage size) during fracturing is inherent in heterogeneous materials, such as composites, concrete, rocks, etc., in which multi-site damaging takes place. Fracturing brittle homogeneous materials do not exhibit this phenomenon due to the lack of pre-failure damage accumulation at the microscopic scale level. This work is to determine the role of structural heterogeneity in the process of primary defect nucleation occurring in conventional homogeneous materials. We present highly resolved time series of fractoluminescence (FL) emitted during multiple chemical bond breakage in shock-damaged silica glass and single crystals \(\upalpha \hbox {-SiO}_{2}\) and \(\upalpha \hbox {-SiC}\). The statistical analysis of the time series has shown that the energy distributions of FL pulses followed the power law indicative of long-range interactions between primary damage events. This scaling phenomenon is caused by the multiplicity of newly formed damaged sites at the level of structural heterogeneity. At the same time, the microscopic and larger damage formation reflected in the acoustic emission time series did not exhibit the presence of long-range interactions between growing brittle cracks.

The Interactions Of Secondary Structural Elements In The Achitecture Of Membrane Proteins

Membrane proteins exist in an anisotropic environment which strongly influences their architecture, stability and folding. Previous studies have mainly focused on the transmembrane domains of alpha helical membrane proteins. However it is becoming increasingly apparent that their architecture is richer than a simple bundle of transmembrane alpha-helices, notably due to helix deformations and other membrane embedded structures. Here, we make use of available databases and tools to investigate the weight and role of structural heterogeneity in the supra molecular organization of membrane proteins.

Analogue models of basin inversion by transpression: role of structural heterogeneity

Abstract The process of faulting within a crustal-scale rift basin, subjected to transpression, is simulated in a series of small-scale experiments using sand and silicone layers. The structural scenario involved three stages: (1) extension; (2) sedimentation; (3) coeval shortening and strike-slip motion. A sandpack, placed above a basal silicone layer, was submitted to extension and produced a system of horst and grabens. Following the extension phase, the resulting surface topography was covered with silicone material, thus introducing a potential décollement between the pre- and post-rift sediments. These latter strata were made of sand. After sedimentation, deformation by transpression was applied using the same amount of shortening and an increasing strike-slip displacement in the different experiments. The strain partitioning increased with the amount of horizontal shear, and strike-slip faults developed at the more advanced stages of transpression. Two phases of faulting were observed before the horst and graben faults could be reactivated. The first phase was characterized by conjugate reverse faults, striking parallel to the rift-bounding faults, compatible with a stress regime in compression. A second phase of faulting was recognized at the end of transpression, leading to the generation of Riedel R-type strike-slip faults. The stress regimes responsible for the kinematics of fault generation and reactivation were interpreted using the Coulomb failure criterion and assumed a friction angle of 30° for the undisturbed sand. The reactivation of the steep normal faults in the horst and graben occurred only after a large strike-slip displacement. The general sequence of fault generation and reactivation suggested a temporal change in the stress regime. This change was caused by the permutation of the minimum and the intermediate principal stress axes and also by a progressive rotation, in the horizontal plane, of the axis of the maximum compressive stress. The spatial variation of the stress regime was also strongly controlled by the geometry of the interbedded silicone layer. A regular and undeformed post-rift silicone layer introduced a more efficient mechanical decoupling between the post-rift cover and the stretched basin. In summary, when a pre-existing graben was present, there was a succession of two distinct ‘tectonic phases’, whereas without a rift, the resulting fault kinematics reflected a single stress state and one tectonic phase.

Role of Structural Heterogeneities on Segmental Orientation in Deformed Chains: Application to Alternating Copolymers

Effects of intrinsic structural and conformational properties on segmental orientation in uniaxially deformed copolymers are considered. Depedence of segmental orientation on equilibrium values of bond angles, torsional states, and probability distribution of rotameric states is studied. Calculations are carried out for chains with independent as well as pairwise interdependent rotameric states for neighboring bonds using the matrix generation technique of rotational isomeric state formalism. Results invite attention to the importance of specific energy and geometry parameters in prescribing the level of molecular orientation in the two diierent components A and B of AB type copolymers. Results are interpreted with reference to polarized Fourier transform infrared spectroscopy measurements in which the orientation of transition moment vectors is detected. The consequences of certain assumptions in data interpretation such as the choice of cylindrically symmetric reference axes along the chain contour are pointed out. The orientations of vectors along the backbone exhibit strong nonlinear dependence on the conformational characteristics of the component A or B to which they are appended. Thus, the bond vectors of the two monomeric units may exhibit quite distinct orientations, arising only from slight perturbation in bond angles of one of the units. Vectors perpendicular to chain backbone were less sensitive to monomeric structure. Calculations carried out independently by Monte Carlo simulations showed that this method yields an adequate qualitative description of the orientational behavior of chain segments while precise quantitative determination requires the use of the exact matrix generation technique.