Biology subjects

Song, C.

Publications and source records attributed to Song, C..

At least 109 records · Page 6Linked to original sources

bioRxiv2023

Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic mice

Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass are reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with 13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, targeted overexpression of Hif1a or Pfkfb3 in osteoblasts of T2D mice averts bone loss. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.

physiology↗

bioRxiv2023

Protein aggregation in plant mitochondria inhibits translation and induces an NAC017-dependent ethylene-associated unfolded protein response

Loss of Lon1 in plant mitochondria led to stunted plant growth and accumulation of nuclear-encoded mitochondrial proteins, including Lon1 substrates, while mitochondrial-encoded proteins typically decreased in abundance. Lon1 mutants contained protein aggregates in the mitochondria matrix which were enriched in PPR-containing proteins and ribosomal subunits of the translation apparatus and were slowed in mitochondrial RNA splicing, editing and general translation rate. Transcriptome analysis showed multiple organellar unfolded protein responses involving ethylene biosynthesis were induced by either Lon1 loss, mitochondrial ribosomal protein loss, translation or respiratory inhibition and most were regulated by the mitochondrial retrograde signaling pathway dependent on the transcription factor NAC017. The short hypocotyl in lon1 mutants during skotomorphogenesis was partially rescued by ethylene inhibitors and mutants showed higher ethylene production rates than wildtype. Together this provides multiple steps in the link between loss of Lon1 and its whole plant phenotype. Single Sentence SummaryLon1 knockout inhibits mitochondrial-encoded gene translation and induces retrograde signaling involving unfolded protein responses.

plant biology↗

bioRxiv2022

Reconceptualizing beta diversity: a hypervolume geometric approach

Beta diversity--the variation among community compositions in a region--is a fundamental measure of biodiversity. Despite a diverse set of measures to quantify beta diversity, most measures have posited that beta diversity is maximized when each community has a single distinct species. However, this assumption overlooks the ecological significance of species interactions and non-additivity in ecological systems, where the function and behaviour of species depend on other species in a community. Here, we introduce a geometric approach to measure beta diversity as the hypervolume of the geometric embedding of a metacommunity. This approach explicitly accounts for non-additivity and captures the idea that introducing a unique, species-rich community composition to a metacommunity increases beta diversity. We show that our hypervolume measure is closely linked to and naturally extends previous information- and variation-based measures while providing a unifying geometric framework for widely adopted extensions of beta diversity. Applying our geometric measures to empirical data, we address two long-standing questions in beta diversity research--the latitudinal pattern of beta diversity and the effect of sampling effort--and present novel ecological insights that were previously obscured by the limitations of traditional approaches. In sum, our geometric approach reconceptualizes beta diversity, offering an alternative and complementary perspective to previous measures, with immediate applicability to existing data.

ecology↗

bioRxiv2022

The photosystem I supercomplex from a primordial green alga Ostreococcus tauri harbors three light-harvesting complex trimers

As a ubiquitous picophytoplankton in the ocean and an early-branching green alga, Ostreococcus tauri is a model prasinophyte species for studying the functional evolution of the light-harvesting systems in photosynthesis. Here, we report the structure and function of the O. tauri photosystem I (PSI) supercomplex in the low light, where it expands its photon-absorbing capacity by assembling with the light-harvesting complexes I (LHCI) and a prasinophyte-specific light-harvesting complex (Lhcp). Its architecture exhibits hybrid features of the plant-type and the green algal-type PSI supercomplexes, consisting of a PSI core, a Lhca1-Lhca4-Lhca2-Lhca3 belt attached on one side and a Lhca5-Lhca6 heterodimer associated on the other side between PsaG and PsaH. Interestingly, nine Lhcp subunits, including one Lhcp1 monomer with a phosphorylated amino-terminal threonine and eight Lhcp2 monomers, oligomerize into three trimers and associate with PSI on the third side between Lhca6 and PsaK. The Lhcp1 phosphorylation and the light-harvesting capacity of PSI were subjected to reversible photoacclimation, suggesting that the formation of OtPSI-LHCI-Lhcp supercomplex is likely due to a state transition-like mechanism induced by light intensity change. Notably, this supercomplex did not exhibit far-red peaks in the 77 K fluorescence spectra, which is possibly due to weak coupling of the chlorophyll a603-a609 pair in OtLhca1-4.

plant biology↗

bioRxiv2022

CRISPR/FnCas12a-mediated efficient multiplex and iterative genome editing in bacterial plant pathogens without donor DNA templates

CRISPR-based genome editing technology is revolutionizing prokaryotic research, but it has been rarely studied in bacterial plant pathogens. Here, we have developed a targeted genome editing method with no requirement of donor templates for convenient and efficient gene knockout in Xanthomonas oryzae pv. oryzae (Xoo), one of the most important bacterial pathogens on rice, by employing the heterogenous CRISPR/Cas12a from Francisella novicida and NHEJ proteins from Mycobacterium tuberculosis. FnCas12a nuclease generated both small and large DNA deletions at the target sites as well as it enabled multiplex genome editing, gene cluster deletion and plasmid cure in the Xoo PXO99A strain. Accordingly, a non-TAL effector-free polymutant strain PXO99AD25E, which lacks all 25 Xop genes involved in Xoo pathogenesis, has been engineered through iterative genome editing. Whole-genome sequencing analysis indicated that FnCas12a did not have a noticeable off-target effect. In addition, we revealed that these strategies are also suitable for targeted genome editing in another bacterial plant pathogen Pseudomonas syringae pv. tomato (Pst). We believe that our bacterial genome editing method will greatly expand the CRISPR study on microorganisms and advance our understanding of the physiology and pathogenesis of Xoo.

microbiology↗

bioRxiv2022

Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

ObjectivesOur objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. MethodsAutopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue. ResultsWe observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. ConclusionsOur results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19. Condensed AbstractSARS-CoV-2 is linked to thrombotic and cardiovascular events; however, the mechanism remains uncertain. Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Autopsy-derived coronary arterial and cardiac tissues from control and COVID-19 patients underwent spatial transcriptomic profiling. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. We observed unique, pro-inflammatory expression profiles among all COVID-19 patients. While heterogeneous viral expression was noted within the tissue, SARS-CoV-2 tended to colocalize with CD31 positive cells within coronary capillaries and was associated with unique expression profiles. Similar patterns were not observed in larger coronary vessels. Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. Such results diminish coronary arterial endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19 infection. LIST OF HIGHLIGHTSO_LISARS-CoV-2 has variable expression patterns within the myocardium of COVID-19 patients C_LIO_LISARS-CoV-2 infection induces a unique myocardial transcriptional programming independent of local viral burden C_LIO_LISARS-CoV-2 myocarditis is predominantly associated with capillaritis, and tissues directly infected with SARS-CoV-2 have unique, pro-inflammatory expression profiles C_LIO_LIDiffuse endothelial activation of larger coronary vessels was absent, diminishing large artery endotheliitis as a significant contributor to cardiovascular events during COVID-19 infection. C_LI

pathology↗

bioRxiv2022

Calcium binding and permeation in TRPV channels: insights from molecular dynamics simulations

Some calcium channels selectively permeate Ca2+, despite the high concentration of monovalent ions in the surrounding environment, which is essential for many physiological processes. Without atomistic and dynamical ion permeation details, the underlying mechanism of Ca2+ selectivity has long been an intensively studied, yet controversial, topic. This study takes advantage of the homologous Ca2+-selective TRPV6 and non-selective TRPV1 and utilizes the recently solved open-state structures and a newly developed multi-site calcium model to investigate the ion binding and permeation features in TRPV channels by molecular dynamics simulations. Our results revealed that the open-state TRPV6 and TRPV1 show distinct ion-binding patterns in the selectivity filter, which lead to different ion permeation features. Two Ca2+ ions simultaneously bind to the selectivity filter of TRPV6 compared with only one Ca2+ in case of TRPV1. Multiple Ca2+ binding at the selectivity filter of TRPV6 permeated in a concerted manner, which could efficiently block the permeation of Na+. Cations of various valences differentiate between the binding sites at the entrance of the selectivity filter in TRPV6. Ca2+ preferentially binds to the central site with a higher probability of permeation, repelling Na+ to a peripheral site. Therefore, we believe that ion binding competition at the selectivity filter of calcium channels, including the binding strength and number of binding sites, determines Ca2+ selectivity under physiological conditions. Additionally, our results showed that pore helix flexibility and the cytosolic domain of TRPV channels regulate ion permeability.

biophysics↗

bioRxiv2022

DBERlibR: Automated Data Analysis for Discipline-Based Education Research

Discipline-Based Education Research (DBER) scientists repeatedly analyze assessment data to ensure question items reliability and examine the efficacy of a new educational intervention. Analyzing assessment data comprises multiple steps and statistical techniques that consume much of researchers time and are error-prone. While education research continues to grow across many disciplines of science, technology, engineering, and mathematics (STEM), the DBER community lacks tools to streamline education research data analysis. DBERlibR--an R package to streamline and automate DBER data processing and analysis--fills this gap. The package reads user-provided assessment data, cleans them, merges multiple datasets (as necessary), checks assumption(s) for specific statistical techniques (as necessary), applies various statistical tests (e.g., one-way analysis of covariance, one-way repeated-measures analysis of variance), and presents and interprets the results all at once. By providing the most frequently used analytic techniques, this package will contribute to DBER by facilitating the creation and widespread use of evidence-based knowledge and practices. The outputs contain a sample interpretation of the results for users convenience. User inputs are minimal; they only need to prepare the data files as instructed and type a function in RStudio to conduct a specific data analysis.

scientific communication and education↗

bioRxiv2022

Six states of Enterococcus hirae V-type ATPase reveals non-uniform rotor rotation during turnover

The vacuolar-type ATPase from Enterococcus hirae (EhV-ATPase) is a thus-far unique adaptation of V-ATPases, as it performs Na+ transport and demonstrates an off-axis rotor assembly. Recent single molecular studies of the isolated V1 domain have indicated that there are subpauses within the three major states of the pseudo three-fold symmetric rotary enzyme. However, there was no structural evidence for these. Herein we activated the EhV-ATPase complex with ATP and identified multiple structures consisting of a total of six states of this complex by using cryo-electron microscopy. The orientations of the rotor complex during turnover, especially in the intermediates, were not as perfectly uniform as expected. The densities in the nucleotide binding pockets in the V1 domain indicated the different catalytic conditions for the six conformations. The off-axis rotor and its interactions with the stator a-subunit during rotation suggests that this non-uniform rotor rotation is performed through the entire complex.

molecular biology↗

bioRxiv2022

Complexes of tubulin oligomers and tau form an intervening network cross-bridging microtubules into bundles

The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) that are implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. While the role of tau in MT bundling is poorly understood, tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in response to varying concentrations of divalent cations (Mg2+ or Ca2+) in dissipative reaction mixtures containing {beta}-tubulin, full-length tau, and GTP at 37{degrees}C. A concentration-time kinetic phase diagram generated by synchrotron small-angle X-ray scattering (SAXS) reveals a wide-spacing MT bundle phase (Bws), a transient intermediate MT bundle phase (Bint), and a tubulin ring phase. Remarkably, SAXS analysis combined with TEM of plastic embedded samples provides direct evidence of an intervening network (IN) of complexes of tubulin oligomers and tau ({approx}5 nm wide filaments), which stabilize MT bundles. In this model, {beta}-tubulin oligomers in the IN are crosslinked by taus MT binding repeats, which also link {beta}-tubulin oligomers to {beta}-tubulin within the MT lattice. The finding of a new role for tubulin revises current dogma where cross-bridging of MTs is attributed entirely to interactions between MAPs. The tubulin-tau complexes of the IN should enhance the barrier properties of MT fascicles in preventing tau missorting to the somatodendritic compartment as happens during neurodegeneration. Furthermore, tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau promoting nucleation and growth of tau fibrils in tauopathies. Significance StatementA cell free model of microtubule (MT) bundles of the axon-initial-segment (known as MT fascicles) was studied in physiologically relevant buffer conditions. MT fascicles have a role in retaining neuronal protein tau, a key protein stabilizing MTs, in the axon. X-ray scattering and electron microscopy led to the discovery of complexes of tubulin oligomers and tau as building blocks of an intervening network that cross-bridge MTs into stable bundles with precisely the same linear geometry observed in-vivo in neurons. Significantly, changes to the chemical structure of tau because of abnormal interactions with cellular enzymes, would be predicted to disrupt the intervening tubulin-tau network and the MT-fascicles barrier function, promoting leakage of tau to the somatodendritic compartment and neuron degradation.

biophysics↗

bioRxiv2022

Rapid monitoring for ecological persistence

Effective conservation of ecological communities requires accurate and up-to-date information about whether species are persisting or declining to extinction. The persistence of ecological communities is largely supported by its structured architecture of species interactions, known as an ecological network. While the persistence of the network supporting the whole community is the most relevant scale for conservation, in practice, we can only monitor small subsets of these networks due to logistical sampling constraints. There is therefore an urgent need to establish links between the small snapshots of data conservationists are able to collect, and the big picture conclusions about ecosystem health demanded by policy makers, scientists and societies. Here we show that the persistence of small subnetworks in isolation -- that is, their persistence when considered separately from the larger network of which they are a part -- is a reliable probabilistic indicator of the persistence of the network as a whole. Our results are general across both antagonistic and mutualistic interaction networks. Empirically, we show that our theoretical predictions are supported by data on invaded networks in restored and unrestored areas, even in the presence of environmental variability. Our work suggests that coordinated action to aggregate information from incomplete sampling can provide a means to rapidly assess the persistence of entire ecological networks and the expected success of restoration strategies. This could significantly improve our ability to monitor progress towards achieving policy targets, such as those enshrined in the UN Convention on Biological Diversity.

ecology↗

bioRxiv2022

Modeling and Inference Methods for Switching Regime-Dependent Dynamical Systems with Multiscale Neural Observations

Realizing neurotechnologies that enable long-term neural recordings across multiple spatial-temporal scales during naturalistic behaviors requires new modeling and inference methods that can simultaneously address two challenges. First, the methods should aggregate information across all activity scales from multiple recording sources such as spiking and field potentials. Second, the methods should detect changes in the regimes of behavior and/or neural dynamics during naturalistic scenarios and long-term recordings. Prior regime detection methods are developed for a single scale of activity rather than multiscale activity, and prior multiscale methods have not considered regime switching and are for stationary cases. Here, we address both challenges by developing a Switching Multiscale Dynamical System model and the associated filtering and smoothing methods. This model describes the encoding of an unobserved brain state in multiscale spike-field activity. It also allows for regime-switching dynamics using an unobserved regime state that dictates the dynamical and encoding parameters at every time-step. We also design the associated switching multiscale inference methods that estimate both the unobserved regime and brain states from simultaneous spike-field activity. We validate the methods in both extensive numerical simulations and prefrontal spike-field data recorded in a monkey performing saccades for fluid rewards. We show that these methods can successfully combine the spiking and field potential observations to simultaneously track the regime and brain states accurately. Doing so, these methods lead to better state estimation compared with single-scale switching methods or stationary multiscale methods. These modeling and inference methods effectively incorporate both regime-detection and multiscale observations. As such, they could facilitate investigation of latent switching neural population dynamics and improve future brain-machine interfaces by enabling inference in naturalistic scenarios where regime-dependent multiscale activity and behavior arise.

neuroscience↗

bioRxiv2022

Exploring the alternative conformation of a known protein structure based on contact map prediction

The rapid development of deep learning-based methods has considerably advanced the field of protein structure prediction. The accuracy of predicting the 3D structures of simple proteins is comparable to that of experimentally determined structures, providing broad possibilities for structure-based biological studies. Another critical question is whether and how multistate structures can be predicted from a given protein sequence. In this study, analysis of multiple two-state proteins demonstrated that deep learning-based contact map predictions contain structural information on both states, which suggests that it is probably appropriate to change the target of deep learningbased protein structure prediction from one specific structure to multiple likely structures. Furthermore, by combining deep learning- and physics-based computational methods, we developed a protocol for exploring alternative conformations from a known structure of a given protein, by which we successfully approached the holo-state conformation of a leucine-binding protein from its apo-state structure.

biophysics↗

bioRxiv2022

Separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis

The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogues with Bub1 being a kinase while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1-PP2A-B56 complex can supports chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation resulting in reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment.

cell biology↗

bioRxiv2022

WDR47 facilitates cell-specific ciliogenesis by modulating intraflagellar transport

Cilia are conserved organelles found in many cell types in eukaryotes, and their dysfunction causes defects in environmental sensing and signaling transduction; such defects are termed ciliopathies. Distinct cilia have cell-specific morphologies and exert distinct functions. However, the underlying mechanisms of cell-specific ciliogenesis and regulation are unclear. Here we identified a WD40-repeat (WDR) protein, WDR47/NMTN-1, and show that it is specifically required for ciliogenesis of AWB chemosensory neurons in C. elegans. WDR47/NMTN-1 is expressed in the AWB chemosensory neuron pair, and is localized at the basal body (BB) of the AWB cilia. Knockout of wdr47/nmtn-1 causes abnormal AWB neuron cilia morphology, structural integrity, and induces aberrant AWB-mediated aversive behaviors. We further demonstrate that wdr47/nmtn-1 deletion affects movement of intraflagellar transport (IFT) particles and their cargo delivery in AWB neurons. Our results indicate that WDR47/NMTN-1 is essential for AWB neuron ciliary morphology and function, which reveal a novel mechanism for cell-specific ciliogenesis. Since WDR47/NMTN-1 is conserved in mammals, our findings may help understand the process of cell-specific ciliogenesis and provide insights for treating ciliopathies.

developmental biology↗

bioRxiv2022

Sequence Analysis of WRKY Transcription Factor Family in Dendrobium officinale

WRKY transcription factors are a key class of plant regulators that regulate Dendrobium growth, development, and stress tolerance. In this work, 74 Dendrobium WRKY genes were found in the Dendrobium whole genome file using tbtools software, hmmer3.0 software, pfam website, mega6.0 software, genedoc software, meme online analysis website, and other tools, and tbtools software was utilized after amino acid alignment. A phylogenetic tree of the Dendrobium and Arabidopsis WRKY transcription factors sequence alignment was built, as well as the chromosomal location, gene structure analysis, conserved domain analysis, and cis-acting element analysis of the Dendrobium WRKY gene. The phylogenetic tree comparison analysis revealed that Dendrobium WRKY transcription factors were classified into three groups: I, II, and III, with Group II subdivided into five subgroups: II-a, II-b, II-c, II-d, and II-e. According to amino acid alignment research, the Dendrobium WRKY transcription factor contains a highly conserved WRKYGQK sequence. According to gene chromosomal mapping, the Dendrobium WRKY gene was found to be irregularly distributed across many chromosomes of Dendrobium officinale. Introns vary greatly in terms of quantity and starting place. According to conserved domain analysis, the Dendrobium WRKY gene comprised diverse patterns in number and species, but all had the conserved domain WRKYGQK, and there were certain distinguishing motifs amongst subfamilies. Elements with a cis-action It was found that the Dendrobium WRKY gene has a lot of cis-acting elements, like light response, low temperature stress response, drought response, hormone response, growth differentiation responses.

bioinformatics↗

bioRxiv2022

Characterization of alkaloids and metabolic intermediates from Dendrobium officinale induced by methyl jasmonate

JA signaling plays a pivotal role in plant stress responses and secondary metabolism. Many studies have demonstrated that jasmonates effectively induce the expressions of alkaloid biosynthesis genes in various plants, which rendered to the accumulation of alkaloid to counteract stresses. Despite the multiple roles of jasmonate (JA) in the regulation of plant growth and different stresses, less studied involved in the regulatory role of JA in D. officinale alkaloids. A strategy for the rapid identification of alkaloid and the intermediates of D. officinale was established based on a solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry method. By using SPE-HPLC-LTQ-Orbitrap method, the potential compounds were tentatively identified by aligning the accurate molecular weight with the METLIN and Dictionary of Natural Products databases. The chemical structures and main characteristic fragments of the potential compounds were further confirmed by retrieving the multistage mass spectra from the MassBank and METLIN databases.The Mass Frontier software was used to speculate the fragmentation pathway of the identified compounds. Seven alkaloids were separated and identified from D. officinale, which were mainly classified into five types (tropane alkaloids, tetrahydroisoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids and spermidine alkaloids). Besides the alkaloids, forty-nine chemical substances, including guanidines, nucleotides, dipeptides, sphingolipids and nitrogen-containing glucosides, were concurrently identified. These findings gives the composition of chemicals currently found in D. officinale, which could provide the scientific method for the identification of alkaloids in other Dendrobium plants.

plant biology↗

bioRxiv2022

Toward an atomistic model of SARS-CoV-2

The causative pathogen of Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enveloped virus assembled by a lipid envelope and multiple structural proteins. In this study, by integrating experimental data, structural modeling, and coarse-grained molecular dynamics simulations, we constructed multiscale models of SARS-CoV-2. Our 500-ns coarse-grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane-embedded proteins and the surrounding lipid molecules in situ. Our results indicated that the membrane-embedded proteins are highly dynamic, and certain types of lipids exhibit various binding preferences to specific sites of the membrane-embedded proteins. The equilibrated virion model was transformed into atomic resolution, which provided a 3D structure for scientific demonstration and can serve as a framework for future exascale all-atom MD simulations.

biophysics↗