Mechanical Performance of Graphene-Based Artificial Nacres under Impact Loads: A Coarse-Grained Molecular Dynamic Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu N
PROVIDER: S-EPMC6432097 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Electrostatic interactions play a pivotal role in many biomolecular processes. The molecular organization and function in biological systems are largely determined by these interactions. Owing to the highly negative charge of RNA, the effect is expected to be more pronounced in this system. Moreover, RNA base pairing is dependent on the charge of the base, giving rise to alternative secondary and tertiary structures. The equilibrium between uncharged and charged bases is regulated by the solution pH, which is therefore a key environmental condition influencing the molecule's structure and behaviour. By means of constant-pH Monte Carlo simulations based on a fast proton titration scheme, coupled with the coarse-grained model HiRE-RNA, molecular dynamic simulations of RNA molecules at constant pH enable us to explore the RNA conformational plasticity at different pH values as well as to compute electrostatic properties as local pK a values for each nucleotide.
| S-EPMC6501344 | biostudies-literature
Project description:Graphene foams (GrFs) have been widely used as structural and/or functional materials in many practical applications. They are always assembled by thin and thick graphene sheets with multiple thicknesses; however, the effect of this basic structural feature has been poorly understood by existing theoretical models. Here, we propose a coarse-grained bi-modal GrF model composed of a mixture of 1-layer flexible and 8-layer stiff sheets to study the mechanical properties and deformation mechanisms based on the mesoscopic model of graphene sheets (Model. Simul. Mater. Sci. Eng. 2011, 19, 54003). It is found that the modulus increases almost linearly with an increased proportion of 8-layer sheets, which is well explained by the mixture rule; the strength decreases first and reaches the minimum value at a critical proportion of stiff sheets ~30%, which is well explained by the analysis of structural connectivity and deformation energy of bi-modal GrFs. Furthermore, high-stress regions are mainly dispersed in thick sheets, while large-strain areas mainly locate in thin ones. Both of them have a highly uneven distribution in GrFs due to the intrinsic heterogeneity in both structures and the mechanical properties of sheets. Moreover, the elastic recovery ability of GrFs can be enhanced by adding more thick sheets. These results should be helpful for us to understand and further guide the design of advanced GrF-based materials.
| S-EPMC8509715 | biostudies-literature
Project description:Intrinsically disordered proteins (IDPs) play crucial roles in cellular regulatory networks and are now recognized to often remain highly dynamic even in specific interactions and assemblies. Accurate description of these dynamic interactions is extremely challenging using atomistic simulations because of the prohibitive computational cost. Efficient coarse-grained approaches could offer an effective solution to overcome this bottleneck if they could provide an accurate description of key local and global properties of IDPs in both unbound and bound states. The recently developed hybrid-resolution (HyRes) protein model has been shown to be capable of providing a semiquantitative description of the secondary structure propensities of IDPs. Here, we show that greatly improved description of global structures and transient interactions can be achieved by introducing a solvent-accessible surface area-based implicit solvent term followed by reoptimization of effective interaction strengths. The new model, termed HyRes II, can semiquantitatively reproduce a wide range of local and global structural properties of a set of IDPs of various lengths and complexities. It can also distinguish the level of compaction between folded proteins and IDPs. In particular, applied to the disordered N-terminal transactivation domain (TAD) of tumor suppressor p53, HyRes II is able to recapitulate various nontrivial structural properties compared to experimental results, some of them to a level of accuracy that is almost comparable to results from atomistic explicit solvent simulations. Furthermore, we demonstrate that HyRes II can be used to simulate the dynamic interactions of TAD with the DNA-binding domain of p53, generating structural ensembles that are highly consistent with existing NMR data. We anticipate that HyRes II will provide an efficient and relatively reliable tool toward accurate coarse-grained simulations of dynamic protein interactions.
| S-EPMC9910785 | biostudies-literature
Project description:Many free-energy sampling and quantum mechanics/molecular mechanics (QM/MM) computations on protein complexes have been performed where, by necessity, a single component is studied isolated in solution while its overall configuration is kept in the complex-like state by either rigid restraints or harmonic constraints. A drawback in these studies is that the system's native fluctuations are lost, both due to the change of environment and the imposition of the extra potential. Yet, we know that having both accurate structure and fluctuations is likely crucial to achieving correct simulation estimates for the subsystem within its native larger protein complex context. In this work, we provide a new approach to this problem by drawing on ideas developed to incorporate experimental information into a molecular simulation by relative entropy minimization to a target system. We show that by using linear biases on coarse-grained (CG) observables (such as distances or angles between large subdomains within a protein), we can maintain the protein in a particular target conformation while also preserving the correct equilibrium fluctuations of the subsystem within its larger biomolecular complex. As an application, we demonstrate this algorithm by training a bias that causes an actin monomer (and trimer) in solution to sample the same average structure and fluctuations as if it were embedded within a much larger actin filament. Additionally, we have developed a number of algorithmic improvements that accelerate convergence of the on-the-fly relative entropy minimization algorithms for this type of application. Finally, we have contributed these methods to the PLUMED open source free energy sampling software library.
| S-EPMC5649387 | biostudies-literature
Project description:Axon bundles cross-linked by microtubule (MT) associate proteins and bounded by a shell skeleton are critical for normal function of neurons. Understanding effects of the complexly geometrical parameters on their mechanical properties can help gain a biomechanical perspective on the neurological functions of axons and thus brain disorders caused by the structural failure of axons. Here, the tensile mechanical properties of MT bundles cross-linked by tau proteins are investigated by systematically tuning MT length, axonal cross-section radius, and tau protein spacing in a bead-spring coarse-grained model. Our results indicate that the stress-strain curves of axons can be divided into two regimes, a nonlinear elastic regime dominated by rigid-body like inter-MT sliding, and a linear elastic regime dominated by affine deformation of both tau proteins and MTs. From the energetic analyses, first, the tau proteins dominate the mechanical performance of axons under tension. In the nonlinear regime, tau proteins undergo a rigid-body like rotating motion rather than elongating, whereas in the nonlinear elastic regime, tau proteins undergo a flexible elongating deformation along the MT axis. Second, as the average spacing between adjacent tau proteins along the MT axial direction increases from 25 to 125 nm, the Young's modulus of axon experiences a linear decrease whereas with the average space varying from 125 to 175 nm, and later reaches a plateau value with a stable fluctuation. Third, the increment of the cross-section radius of the MT bundle leads to a decrease in Young's modulus of axon, which is possibly attributed to the decrease in MT numbers per cross section. Overall, our research findings offer a new perspective into understanding the effects of geometrical parameters on the mechanics of MT bundles as well as serving as a theoretical basis for the development of artificial MT complexes potentially toward medical applications.
| S-EPMC8456295 | biostudies-literature
Project description:Tethered bilayer lipid membranes (tBLMs) provide a stable platform for modeling the dynamics and order of biological membranes where the tethers mimic the cytoskeletal supports present in biological cell membranes. In this paper coarse-grained molecular dynamics (CGMD) is applied to study the effects of tethers on lipid membrane properties. Using results from the CGMD model and the overdamped Fokker-Planck equation, we show that the diffusion tensor and particle density of water in the tBLM is spatially dependent. Further, it is shown that the membrane thickness, lipid diffusion, defect density, free energy of lipid flip-flop, and membrane dielectric permittivity are all dependent on the tether density. The numerically computed results from the CGMD model are in agreement with the experimentally measured results from tBLMs containing different tether densities and lipids derived from Archaebacteria. Additionally, using experimental measurements from Escherichia coli bacteria and Saccharomyces Cerevisiae yeast tethered membranes, we illustrate how previous molecular dynamics results can be combined with the proposed model to estimate the dielectric permittivity and defect density of these membranes as a function of tether density.
| S-EPMC5063460 | biostudies-literature
Project description:We propose a simple general framework to predict folding, native states, energy barriers, protein unfolding, as well as mutation induced diseases and other protein structural analyses. The model should not be considered as an alternative to classical approaches (Molecular Dynamics or Monte Carlo) because it neglects low scale details and rather focuses on global features of proteins and structural information. We aim at the description of phenomena that are out of the range of classical molecular modeling approaches due to the large computational cost: multimolecular interactions, cyclic behavior under variable external interactions, and similar. To demonstrate the effectiveness of the approach in a real case, we focus on the folding and unfolding behavior of tropoelastin and its mutations. Specifically, we derive a discrete mechanical model whose structure is deduced based on a coarse graining approach that allows us to group the amino acids sequence in a smaller number of `equivalent' masses. Nearest neighbor energy terms are then introduced to reproduce the interaction of such amino acid groups. Nearest and non-nearest neighbor energy terms, inter and intra functional blocks are phenomenologically added in the form of Morse potentials. As we show, the resulting system reproduces important properties of the folding-unfolding mechanical response, including the monotonic and cyclic force-elongation behavior, representing a physiologically important information for elastin. The comparison with the experimental behavior of mutated tropoelastin confirms the predictivity of the model. STATEMENT OF SIGNIFICANCE: Classical approaches to the study of phenomena at the molecular scale such as Molecular Dynamics (MD) represent an incredible tool to unveil mechanical and conformational properties of macromolecules, in particular for biological and medical applications. On the other hand, due to the computational cost, the time and spatial scales are limited. Focusing of the real case of tropoelastin, we propose a new approach based on a careful coarse graining of the system, able to describe the overall properties of the macromolecule and amenable of extension to larger scale effects (protein bundles, protein-protein interactions, cyclic loading). The comparison with tropoelastin behavior, also for mutations, is very promising.
| S-EPMC8542605 | biostudies-literature
Project description:Systematic bottom-up coarse-graining (CG) of molecular systems provides a means to explore different coupled length and time scales while treating the molecular-scale physics at a reduced level. However, the configuration dependence of CG interactions often results in CG models with limited applicability for exploring the parametrized configurations. We propose a statistical mechanical theory to design CG interactions across different configurations and conditions. In order to span wide ranges of conformational space, distinct classical CG free energy surfaces for characteristic configurations are identified using molecular collective variables. The coupling interaction between different CG free energy surfaces can then be systematically determined by analogy to quantum mechanical approaches describing coupled states. The present theory can accurately capture the underlying many-body potentials of mean force in the CG variables for various order parameters applied to liquids, interfaces, and in principle proteins, uncovering the complex nature underlying the coupling interaction and imparting a new protocol for the design of predictive multiscale models.
| S-EPMC9940719 | biostudies-literature
Project description:The Tumor Necrosis Factor (TNF) and the TNF receptor (TNFR) superfamilies are composed of 19 ligands and 30 receptors, respectively. The oligomeric properties of ligands, both membrane bound and soluble, has been studied most. However, less is known about the oligomeric properties of TNFRs. Earlier reports identified the extracellular, membrane-distal, cysteine-rich domain as a pre-ligand assembly domain which stabilizes receptor dimers and/or trimers in the absence of ligand. Nevertheless, recent reports based on structural nuclear magnetic resonance (NMR) highlight the intrinsic role of the transmembrane domains to form dimers (p75NTR), trimers (Fas), or dimers of trimers (DR5). Thus, understanding the structural basis of transmembrane oligomerization may shed light on the mechanism for signal transduction and the impact of disease-associated mutations in this region. To this end, here we used an in silico coarse grained molecular dynamics approach with Martini force field to study TNFR transmembrane homotypic interactions. We have first validated this approach studying the three TNFR described by NMR (p75NTR, Fas, and DR5). We have simulated membrane patches composed of 36 helices of the same receptor equidistantly distributed in order to get unbiassed information on spontaneous proteins assemblies. Good agreement was found in the specific residues involved in homotypic interactions and we were able to observe dimers, trimers, and higher-order oligomers corresponding to those reported in NMR experiments. We have, applied this approach to study the assembly of disease-related mutations being able to assess their impact on oligomerization stability. In conclusion, our results showed the usefulness of coarse grained simulations with Martini force field to study in an unbiased manner higher order transmembrane oligomerization.
| S-EPMC7859260 | biostudies-literature
Project description:Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
| S-EPMC10796360 | biostudies-literature