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71.
The purpose of the present study was to determine whether zinc and calcium could interact at the tissue level. In the first
part of the study, adult rats were injected with ZnCl2 dissolved in a physiological saline solution to determine the effects of Zn on Ca levels in various tissues. In the second
part of the study, weaned rats (at day 22 postnatally) were fed a diet supplemented with Zn until day 50 and were then sacrificed.
In both instances, blood, brain, heart, liver, and skeletal muscle were taken and analyzed. In the Zn-injected group, the
brain, heart, and liver showed no interaction between Zn and Ca. The skeletal muscle, in contrast, showed a decrease in Ca
in the homogenate, whereas Zn contents showed a significant increase at the sarcoplasmic reticulum (SR). Likewise, in the
Zn-supplemented group, the Zn content of the SR vesicle of the skeletal muscle showed an increase, whereas Ca content of the
pellet (14,000 g), which contains cell debris, nucleus, mitochondria, and SR vesicles of this group, showed a decrease. Current
findings suggest antagonistic effects between Zn and Ca on this tissue. Zn may play a critical role in cellular function through
the alteration of itnracellular distribution of Ca in skeletal muscle. 相似文献
72.
Changes in the composition of a Fagus-Acer (Beech-Sugar maple) forest in southeastern Wisconsin over a 16-yr period from 1971 to 1987 are analyzed in relation to a severe glaze (ice) storm disturbance occurring within the census period. Landscape topography created ‘windward’ and ‘leeward’ forest aspects with respect to storm severity, which resulted in greater canopy opening on the windward aspect. In the tree stratum, most species remained stable in density and most of the common species increased in basal area into larger size classes. However, Fagus grandifolia, Ulmus rubra, and the small tree Ostrya virginiana suffered net losses that suggest synergistic effects between glaze storm disturbance and other factors upon tree mortality. In the sapling stratum, canopy opening strongly promoted release of shade-to levant Acer sac-charum. On the windward forest aspect, sapling densities of less shade-tolerant species also increased, in contrast to the absence of such increases on the leeward forest aspect. In the shrub (regeneration) stratum, species responses were heterogeneous. Regeneration of most species increased over the 16-yr period, and some less shade-tolerant species showed increased regeneration differentially on the windward forest aspect. Overall, disturbance appears to have accelerated forest succession toward increased dominance by A. saccharum and persistence of both Fagus and Tilia americana through their capacities for root sprouting. However, forest succession was retarded somewhat on the windward aspect through increased recruitment of less-shade tolerant species. These results parallel those of other studies of glaze storm disturbance, and they illustrate how spatially heterogeneous disturbance intensity may contribute to maintenance of forest diversity. 相似文献
73.
Fatemeh Rahimi Gharemirshamlu Kourosh Bamdad Sirous Naeimi 《Journal of cellular biochemistry》2019,120(8):14156-14164
In this study we are looking into two contradicting mutations found in prion protein (PrP) viz G127V and D178V, that are reportedly protective and pathogenic, respectively. Despite significant advances in comprehension of the role of pathogenic mutations, the role of protective mutation in amyloid fold inhibition still lacks a substantial basis. To understand the structural basis of protective mutation, molecular dynamics simulation coupled with protein-protein docking and molecular mechanics/Poisson-Boltzmann surface area analysis was used to understand the instant structural variability brought about by these mutations alone and in combination on PrP and prion-prion complex. Atomic-scale investigations successfully revealed that the binding pattern of prion-prion varies differentially in protective and pathogenic mutations with secondary structure showing distinct contrasting patterns, which could supposedly be a critical factor for differential prion behavior in protective and pathogenic mutations. Considering the reported role of an amyloid fold in prion-prion binding, the contrasting pattern has given us a lead in comprehending the role of these mutations and has been used in this study to look for small molecules that can inhibit amyloid fold for prion-prion interaction in pathogenic mutant carrying PrP. 相似文献
74.
Laureano E. Carpio 《Journal of biomolecular structure & dynamics》2020,38(17):5136-5147
AbstractThe Flavivirus genus comprise several important human pathogens, including dengue, West Nile, Yellow fever, Japanese encephalitis, Zika, and tick-borne encephalitis viruses. These enveloped viruses affect more than 2 billion people in the world, mainly in less developed countries. Although some vaccines exist for some flaviviruses, these vaccines are not universally available due to many factors and since their infections are a world-wide public health issue, the development of antiviral molecules is fundamental. Flavivirus membranes, through the help of the envelope E glycoprotein, fuse with endosomal compartments in a pH-dependent way to release their genome into the cytoplasm and require specific lipids, such as bis(monoacylglycero)phosphate (BMP), for efficient fusion. The fundamental role the envelope E protein has on viral entry and membrane fusion suggest that it is an essential antiviral target. In this work, we have used atomistic molecular dynamics simulations to study the binding of the head-group of BMP to the tip of the envelope E proteins of ZIKV, DENV, TBEV and JEV viruses whose three-dimensional structures are known. Our results indicate that, apart from the fusion loop, there are different amino acid residues in different regions of the envelope E proteins of flaviviruses capable of binding the head-group of BMP. These regions should work together to accomplish the binding and fusion of the envelope and endosomal membranes and represent a new target to develop and design potent and effective antiviral agents capable of blocking flavivirus-endosome membrane fusion. 相似文献
75.
76.
Parasuraman Aiya Subramani Venkata Ramireddy Narala R Dinakaran Michael Dakshayani Lomada Madhava C Reddy 《Bioinformation》2015,11(5):248-253
Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho,
Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1.
There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up
selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of
interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin
(from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as
GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized
compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE).
The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis
for curcumin binding to GGTase1 and FTase is reported. 相似文献
77.
Inference of molecular function of proteins is the fundamental task in the quest for understanding cellular processes. The task is getting increasingly difficult with thousands of new proteins discovered each day. The difficulty arises primarily due to lack of high‐throughput experimental technique for assessing protein molecular function, a lacunae that computational approaches are trying hard to fill. The latter too faces a major bottleneck in absence of clear evidence based on evolutionary information. Here we propose a de novo approach to annotate protein molecular function through structural dynamics match for a pair of segments from two dissimilar proteins, which may share even <10% sequence identity. To screen these matches, corresponding 1 µs coarse‐grained (CG) molecular dynamics trajectories were used to compute normalized root‐mean‐square‐fluctuation graphs and select mobile segments, which were, thereafter, matched for all pairs using unweighted three‐dimensional autocorrelation vectors. Our in‐house custom‐built forcefield (FF), extensively validated against dynamics information obtained from experimental nuclear magnetic resonance data, was specifically used to generate the CG dynamics trajectories. The test for correspondence of dynamics‐signature of protein segments and function revealed 87% true positive rate and 93.5% true negative rate, on a dataset of 60 experimentally validated proteins, including moonlighting proteins and those with novel functional motifs. A random test against 315 unique fold/function proteins for a negative test gave >99% true recall. A blind prediction on a novel protein appears consistent with additional evidences retrieved therein. This is the first proof‐of‐principle of generalized use of structural dynamics for inferring protein molecular function leveraging our custom‐made CG FF, useful to all. Proteins 2014; 82:2443–2454. © 2014 Wiley Periodicals, Inc. 相似文献
78.
We apply the recently developed phase integration method (PIM) (Monteferrante et al. Mol Phys. 2011;109:3015–3027) to the calculation of infrared spectra of gas phase molecules. The PIM combines a generalised Monte Carlo sampling of the exact thermal density of the system with classical molecular dynamics to obtain approximate time quantum correlation functions. To describe the molecules, we adopt very simple analytical potentials that have, however, proved interesting, and surprisingly challenging, benchmarks for approximate quantum dynamical schemes. We show that, in contrast with two other commonly applied methods, our spectra do not exhibit spurious features or unphysical shifts depending on the temperature. Identifying the positions of the peaks requires only a few tens of trajectories, while an accurate evaluation of the relative intensities of the peaks is computationally more demanding. 相似文献
79.
Begum Alaybeyoglu Berna Sariyar Akbulut 《Journal of biomolecular structure & dynamics》2016,34(11):2387-2398
Discovery of cargo carrying cell-penetrating peptides has opened a new gate in the development of peptide-based drugs that can effectively target intracellular enzymes. Success in application and development of cell-penetrating peptides in drug design depends on understanding their translocation mechanisms. In this study, our aim was to examine the bacterial translocation mechanism of the cell-penetrating pVEC peptide (LLIILRRRIRKQAHAHSK) using steered molecular dynamics (SMD) simulations. The significance of specific residues or regions for translocation was studied by performing SMD simulations on the alanine mutants and other variants of pVEC. Residue-based analysis showed that positively charged residues contribute to adsorption to the lipid bilayer and to electrostatic interactions with the lipid bilayer as peptides are translocated. Translocation takes place in three main stages; the insertion of the N-terminus into the bilayer, the inclusion of the whole peptide inside the membrane and the exit of the N-terminus from the bilayer. These three stages mirror the three regions on pVEC; namely, the hydrophobic N-terminus, the cationic midsection, and the hydrophilic C-terminus. The N-terminal truncated pVEC, I3A, L5A, R7A mutants and scramble-pVEC make weaker interactions with the lipids during translocation highlighting the contribution of the N-terminal residues and the sequence of the structural regions to the translocation mechanism. This study provides atomistic detail about the mechanism of pVEC peptide translocation and can guide future peptide-based drug design efforts. 相似文献
80.
Tropomyosin (Tpm) is a dimeric coiled-coil protein that binds to filamentous actin, and regulates actin-myosin interaction by moving between three positions corresponding to the blocked, closed, and open states. To elucidate how Tpm undergoes transitions between these functional states, we have built structural models and conducted extensive molecular dynamics simulations of the Tpm-actins/myosin complex in the closed and open states (total simulation time >1.4 μs). Based on the simulation trajectories, we have analyzed the dynamics and energetics of a truncated Tpm interacting with actins/myosin under the physiological conditions. Our simulations have shown distinct dynamics of four Tpm periods (P3-P6), featuring pronounced biased fluctuations of P4 and P5 toward the open position in the closed state, which is consistent with a conformational selection mechanism for Tpm-regulated myosin binding. Additionally, we have identified key residues of Tpm specifically binding to actins/myosin in the closed and open state. Some of them were validated as functionally important in comparison with past functional/clinical studies, and the rest will make promising targets for future mutational experiments. 相似文献