The Effect of Box Shape on the Dynamic Properties of Proteins Simulated under Periodic Boundary Conditions

Abstract: The effect of the box shape on the dynamic behavior of proteins simulated under periodic boundary conditions is evaluated. In particular, the influence of simulation boxes defined by the near-densest lattice packing (NDLP) in conjunction with rotational constraints is compared to that of standard box types without these constraints. Three different proteins of varying size, shape, and secondary structure content were examined in the study. The statistical significance of differences in RMSD, radius of gyration, solvent-accessible surface, number of hydrogen bonds, and secondary structure content between proteins, box types, and the application or not of rotational constraints has been assessed. Furthermore, the differences in the collective modes for each protein between different boxes and the application or not of rotational constraints have been examined. In total 105 simulations were performed, and the results compared using a three-way multivariate analysis of variance (MANOVA) for properties derived from the trajectories and a three-way univariate analysis of variance (ANOVA) for collective modes. It is shown that application of roto-translational constraints does not have a statistically significant effect on the results obtained from the different simulations. However, the choice of simulation box was found to have a small (5-10%), but statistically significant effect on the behavior of two of the three proteins included in the study

Unbreaking Assemblies in Molecular Simulations with Periodic Boundaries

This data set contains all examples shown in figure 2 of the associated manuscript. Every example contains the original GRO, XTC, TPR and a folder called `whole` which contains the whole.gro, whole.xtc and a README with the input parameters. For the Hii example there is also a segmentation folder which contains the output of the leaflet segmentation. Additionally the folders for generating the SI have been added in v1.1. - dipeptides - self-assembly - inverted hexagonal - large vesicle - undulate membrane (SI) - speed comparison (SI)The code for mdvwhole can be installed with `pip install mdvwhole` (python >= 3.8). The code is available at `https://github.com/BartBruininks/mdvwhole`

Competing Roles of Ca²⁺and Nonmuscle Myosin IIA on the Dynamics of the Metastasis-Associated Protein S100A4

The calcium-binding protein S100A4 plays an important role in a wide range of biological processes such as cell motility, invasion, angiogenesis, survival, differentiation, contractility, and tumor metastasis and interacts with a range of partners. To understand the functional roles and interplay of S100A4 binding partners such as Ca2+and nonmuscle myosin IIA (NMIIA), we used molecular dynamics simulations to investigate apo S100A4 and four holo S100A4 structures: S100A4 bound to Ca2+, S100A4 bound to NMIIA, S100A4 bound to Ca2+and NMIIA, and a mutated S100A4 bound to Ca2+and NMIIA. Our results show that two competing factors, namely, Ca2+-induced activation and NMIIA-induced inhibition, modulate the dynamics of S100A4 in a competitive manner. Moreover, Ca2+binding results in enhanced dynamics, regulating the interactions of S100A4 with NMIIA, while NMIIA induces asymmetric dynamics between the chains of S100A4. The results also show that in the absence of Ca2+the S100A4-NMIIA interaction is weak compared to that of between S100A4 bound to Ca2+and NMIIA, which may offer a quick response to dropping calcium levels. In addition, certain mutations are shown to play a marked role on the dynamics of S100A4. The results described here contribute to understanding the interactions of S100A4 with NMIIA and the functional roles of Ca2+, NMIIA, and certain mutations on the dynamics of S100A4. The results of this study could be interesting for the development of inhibitors that exploit the shift of balance between the competing roles of Ca2+and NMIIA

Backmapping triangulated surfaces to coarse-grained membrane models

Many biological processes involve large-scale changes in membrane shape. Computer simulations of these processes are challenging since they occur across a wide range of spatiotemporal scales that cannot be investigated in full by any single current simulation technique. A potential solution is to combine different levels of resolution through a multiscale scheme. Here, we present a multiscale algorithm that backmaps a continuum membrane model represented as a dynamically triangulated surface (DTS) to its corresponding molecular model based on the coarse-grained (CG) Martini force field. Thus, we can use DTS simulations to equilibrate slow large-scale membrane conformational changes and then explore the local properties at CG resolution. We demonstrate the power of our method by backmapping a vesicular bud induced by binding of Shiga toxin and by transforming the membranes of an entire mitochondrion to near-atomic resolution. Our approach opens the way to whole cell simulations at molecular detail

Характеристика механизма функционирования форм хозяйствования с иностранными инвестициями

Механизм функционирования предприятия с иностранными инвестициями неразрывно связан с понятиями "хозяйственный механизм" и "механизм функционирования предприятия". В экономической науке советского периода широко применялся термин "хозяйственный механизм". Рассматривался хозяйственный механизм отдельного предприятия, отрасли, экономики страны в целом, то есть рассматривался хозяйственный механизм экономических систем различного уровня

Asymmetric CorA Gating Mechanism as Observed by Molecular Dynamics Simulations

The CorA family of proteins plays a housekeeping role in the homeostasis of divalent metal ions in many bacteria and archaea as well as in mitochondria of eukaryotes, rendering it an important target to study the mechanisms of divalent transport and regulation across different life domains. Despite numerous studies, the mechanistic details of the channel gating and the transport of the metal ions are still not entirely understood. Here, we use all-atom and coarse-grained molecular dynamics simulations combined with in vitro experiments to investigate the influence of divalent cations on the function of CorA. Simulations reveal pronounced asymmetric movements of monomers that enable the rotation of the α7 helix and the cytoplasmic subdomain with the subsequent formation of new interactions and the opening of the channel. These computational results are functionally validated using site-directed mutagenesis of the intracellular cytoplasmic domain residues and biochemical assays. The obtained results infer a complex network of interactions altering the structure of CorA to allow gating. Furthermore, we attempt to reconcile the existing gating hypotheses for CorA to conclude the mechanism of transport of divalent cations via these proteins