Molecular Dynamics Simulations Research Articles

Exploring the interaction of graphene-based nanomaterials with atherosclerosis-related protein targets: insights from molecular docking and dynamics simulations

Exploring the interaction of graphene-based nanomaterials with atherosclerosis-related protein targets: insights from molecular docking and dynamics simulations

Elastic properties of Fe95-yNb2Mo2Cu1Siy-xBx (x=5-8, y=20-26) at % amorphous alloys

Amorphous materials exhibit complex atomic structures characterized by the absence of long-range order, in contrast to the well-defined periodicity of crystalline materials. This structural complexity is further pronounced in compositions such as FeMCuSiB (M = Nb, Mo, W and Ta), which incorporate elements with varying atomic radii and valencies. The Young's modulus of structures generated using traditional methods, such as melt-quenching and random packing, shows poor agreement with experimental data. In this study, we employ hybrid methods for generating the structures, which involve randomly packing elements without overlap, followed by thermalization at room temperature using Ab-initio Molecular Dynamics simulations. The Young's modulus evaluated from these structures aligns well with values measured using Dynamic Mechanical Analysis. Additionally, we utilize these structures to determine other elastic moduli including the bulk modulus and tetragonal shear modulus and find that the obtained values are consistent with the expected range for these compounds. We attribute the improved accuracy to a more representative approximation of the amorphous structure and the direct application of energy-strain relationships, rather than stress-strain relationships, for elastic moduli determination. Our methodology facilitates reliable predictions of the physical properties of amorphous materials and contributes to the design of FeMCuSiB (M = Nb, Mo, W and Ta) alloys with enhanced mechanical properties.

The adsorption of drugs on nanoplastics has severe biological impact

Micro- and nanoplastics can interact with various biologically active compounds forming aggregates of which the effects have yet to be understood. To this end, it is vital to characterize these aggregates of key compounds and micro- and nanoplastics. In this study, we examined the adsorption of the antibiotic tetracycline on four different nanoplastics, made of polyethylene (PE), polypropylene (PP), polystyrene (PS), and nylon 6,6 (N66) through chemical computation. Two separate approaches were employed to generate relevant conformations of the tetracycline-plastic complexes. In the first approach, we folded the plastic particle from individual polymer chains in the presence of the drug through multiple separate simulated annealing setups. In the second, more biased, approach, the neat plastic was pre-folded through simulated annealing, and the drug was placed at its surface in multiple orientations. The former approach was clearly superior to the other, obtaining lower energy conformations even with the antibiotic buried inside the plastic particle. Quantum chemical calculations on the structures revealed that the adsorption energies show a trend of decreasing affinity to the drug in the order of N66> PS> PP> PE. In vitro experiments on tetracycline-sensitive cell lines demonstrated that, in qualitative agreement with the calculations, the biological activity of tetracycline drops significantly in the presence of PS particles. Preliminary molecular dynamics simulations on two selected aggregates with each plastic served as first stability test of the aggregates under influence of temperature and in water. We found that all the selected cases persisted in water indicating that the aggregates may be stable also in more realistic environments. In summary, our data show that the interaction of micro- and nanoplastics with drugs can alter drug absorption, facilitate drug transport to new locations, and increase local antibiotic concentrations, potentially attenuating antibiotic effect and at the same time promoting antibiotic resistance.

IsRNAcirc: 3D structure prediction of circular RNAs based on coarse-grained molecular dynamics simulation.

As an emerging class of RNA molecules, circular RNAs play pivotal roles in various biological processes, thereby determining their three-dimensional (3D) structure is crucial for a deep understanding of their biological significances. Similar to linear RNAs, the development of computational methods for circular RNA 3D structure prediction is challenging, especially considering the inherent flexibility and potentially long length of circular RNAs. Here, we introduce an extension of our previous IsRNA2 model, named IsRNAcirc, to enable circular RNA 3D structure predictions through coarse-grained molecular dynamics simulations. The workflow of IsRNAcirc consists of four main steps, including input preparation, end closure, structure prediction, and model refinement. Our results demonstrate that IsRNAcirc can provide reasonable 3D structure predictions for circular RNAs, which significantly reduce the locally irrational elements contained in the initial input. Moreover, for a validation test set comprising 34 circular RNAs, our IsRNAcirc can generate 3D models with better scores than the template-based 3dRNA method. These findings demonstrate that our IsRNAcirc method is a promising tool to explore the structural details along with intricate interactions of circular RNAs.

Bioinspired Photothermal Metal-Organic Framework Cocrystal with Ultra-Fast Water Transporting Channels for Solar-Driven Interfacial Water Evaporation.

Herein, a bioinspired metal-organic framework (MOF) cocrystal produced from the co-assembly of a MOF [Ni3(hexaiminobenzene)2, Ni3(HIB)2] and p-chloranils (CHLs) is reported. Because of the 2D conjugation nature and the formation of persistent anion radicals, this cocrystal shows an excellent photothermal property, and is further used as an absorber in solar-driven interfacial water evaporation. The solar-driven interfacial water evaporation rate (4.04 kg m-2 h-1) is among the best compared with those of previously reported photothermal materials. Molecular dynamics simulation results suggested that the rotating of the CHL molecules relative to the MOF planes tuned the pore size to enable the ultra-fast water transporting, and thus ultra-high water transporting rates (1.11 × 1011 and 3.21 × 1011 H2O s-1 channel-1 at 298.2 and 323.0 K, respectively) for layered cocrystal structures, that are much higher than that of aquaporins (≈1.1 × 1010 H2O s-1 channel-1 at 298.2 K), are observed. The superior solar-driven water evaporation performance is thus attributed to the synergistic effect of the ultra-fast water transporting pores together with the excellent photothermal property of the cocrystal. This research provided a biomimetic strategy of rational design and production of charge transfer cocrystals to modulate their pores and photothermal properties for solar-driven interfacial water evaporation.

Molecular dynamics insights into the dynamical behavior of structurally modified water in aqueous deep eutectic solvents (ADES).

Recent studies have demonstrated that the presence of water in deep eutectic solvents (DESs) significantly affects their dynamics, structure, and physical properties. Although the structural changes due to the addition of water are well understood, the microscopic dynamics of these changes have been rarely studied. Here, we performed molecular dynamics simulation of 30% (v/v) (∼0.57 molar fraction) water mixture of DES containing CH3CONH2 and NaSCN/KSCN at various salt fractions to understand the microscopic structure and dynamics of water. The simulated results reveal a heterogeneous environment for water molecules in aqueous DES (ADES), which is influenced by the nature of the cation. The diffusion coefficients of water in ADESs are significantly lower than that in neat water and concentrated aqueous NaSCN/KSCN solution. When Na+ ions are replaced by K+ ions in the ADES system, the diffusion coefficient increases, which is consistent with the measured nuclear magnetic resonance data. Self-dynamic structure factor for water and other simulated dynamic quantities, such as reorientation, hydrogen-bond, and residence time correlation functions, show markedly slower dynamics inside ADES than in the neat water and aqueous salt solution. Moreover, these dynamics become faster when Na+ ions in ADES are replaced by K+ ions. The results suggest that the structural environment of water in Na+-rich ADES is rigid due to the presence of cation-bound water and geometrically constrained water. The medium becomes less rigid as the KSCN fraction increases due to the relatively weaker interaction of K+ ions with water than Na+ ions, which accelerates the dynamical processes.

Proton transfer driven by the fluctuation of water molecules in chitin film.

Proton-transfer mechanisms and hydration states were investigated in chitin films possessing the functionality of fuel-cell electrolytes. The absolute hydration number per chitin molecule (N) as a function of relative humidity (RH) was determined from the OH stretching bands of H2O molecules, and the proton conductivity was found to enhance above N = 2 (80%RH). The FIR spectrum at 500-900cm-1 for 20%RH (N < 1) together with first-principles calculations clearly shows that the w1 site has the same hydration strength as the w2 site. The molecular dynamics simulations for N = 2 demonstrate that H2O molecules with tiny fluctuations are localized on w1 and w2, and the hydrogen-bond (HB) network is formed via the CH2OH group of chitin molecules. Shrinkage of the O-O distance (dOO), which synchronizes with the barrier height, is required for proton transfer from H3O+ to adjacent CH2OH groups or H2O molecules. Nevertheless, dOO is hardly modulated for N = 2 because H2O molecules are strongly constrained on w1 and w2, and therefore, the transfer probability becomes small. For N = 3, novel HBs emerged between the additional H2O molecules broadly distributed on the w3 site and H2O molecules on w1 and w2. The transfer probability is enhanced because large fluctuations and diffusions in the whole H2O molecule yield large modulations of dOO. Consequently, long-range proton hopping is driven by the Zundel-type protonated hydrates in the water network.

In-silico and in-vitro study of novel antimicrobial peptide AM1 from Aegle marmelos against drug-resistant Staphylococcus aureus

Antimicrobial peptides have garnered increasing attention as potential alternatives due to their broad-spectrum antimicrobial activity and low propensity for developing resistance. This is for the first time; proteome sequences of Aegle marmelos were subjected to in-silico digestion and AMP prediction were performed using DBAASP server. After screening the peptides on the basis of different physiochemical property, peptide sequence GKEAATKAIKEWGQPKSKITH (AM1) shows the maximum binding affinity with − 10.2 Kcal/mol in comparison with the standard drug (Trimethoprim) with − 7.4 kcal/mol and − 6.8 Kcal/mol for DHFR and SaTrmK enzyme respectively. Molecular dynamics simulation performed for 300ns, it has been found that peptide was able to stabilize the protein more effectively, analysed by RMSD, RMSF, and other statistical analysis. Free binding energy for DHFR and SaTrmK interaction from MMPBSA analysis with peptide was found to be -47.69 and − 44.32 Kcal/mol and for Trimethoprim to be -13.85 Kcal/mol and − 11.67 Kcal/mol respectively. Further in-vitro study was performed against Methicillin Susceptible Staphylococcus aureus (MSSA), Methicillin Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant Staphylococcus aureus (MDR-SA) strain, where MIC values found to be 2, 4, and 8.5 µg/ml lesser in comparison to trimethoprim which has higher MIC values 2.5, 5, and 9.5 µg/ml respectively. Thus, our study provides the insight for the further in-vivo study of the peptides against multi-drug resistant S. aureus.

Novel dual-pathogen multi-epitope mRNA vaccine development for Brucella melitensis and Mycobacterium tuberculosis in silico approach.

Brucellosis and Tuberculosis, both of which are contagious diseases, have presented significant challenges to global public health security in recent years. Delayed treatment can exacerbate the conditions, jeopardizing patient lives. Currently, no vaccine has been approved to prevent these two diseases simultaneously. In contrast to traditional vaccines, mRNA vaccines offer advantages such as high efficacy, rapid development, and low cost, and their applications are gradually expanding. This study aims to develop multi-epitope mRNA vaccines argeting Brucella melitensis and Mycobacterium tuberculosis H37Rv (L4 strain) utilizing immunoinformatics approaches. The proteins Omp25, Omp31, MPT70, and MPT83 from the specified bacteria were selected to identify the predominant T- and B-cell epitopes for immunological analysis. Following a comprehensive evaluation, a vaccine was developed using helper T lymphocyte epitopes, cytotoxic T lymphocyte epitopes, linear B-cell epitopes, and conformational B-cell epitopes. It has been demonstrated that multi-epitope mRNA vaccines exhibit increased antigenicity, non-allergenicity, solubility, and high stability. The findings from molecular docking and molecular dynamics simulation revealed a robust and enduring binding affinity between multi-epitope peptides mRNA vaccines and TLR4. Ultimately, Subsequently, following the optimization of the nucleotide sequence, the codon adaptation index was calculated to be 1.0, along with an average GC content of 54.01%. This indicates that the multi-epitope mRNA vaccines exhibit potential for efficient expression within the Escherichia coli(E. coli) host. Analysis through immune modeling indicates that following administration of the vaccine, there may be variation in immunecell populations associated with both innate and adaptive immune reactions. These types encompass helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), regulatory T lymphocytes, natural killer cells, dendritic cells and various immune cell subsets. In summary, the results suggest that the newly created multi-epitope mRNA vaccine exhibits favorable attributes, offering novel insights and a conceptual foundation for potential progress in vaccine development.

Rational Design for Enhancing Cellobiose Dehydrogenase Activity and Its Synergistic Role in Straw Degradation.

Addressing the demand for efficient biological degradation of straw, this study employed rational design coupled with structural biology and enzyme engineering techniques to enhance the catalytic activity of cellobiose dehydrogenase (PsCDH, CDH form Pycnoporus sanguineus). By predicting and modifying the active site and key amino acids of PsCDH, several CDH immobilized enzyme preparations with higher catalytic activities were successfully obtained. The excellent mutant T1 (C286Y/A461H/F464R) exhibited a 2.7-fold increase in enzyme activity compared to the wild type. Simulated calculations indicated that the enhancement of catalytic activity was primarily due to the formation of additional intermolecular interactions between CDH and the substrate, as well as the enlargement of the substrate pocket to reduce steric hindrance effects. Additionally, molecular dynamics simulation analysis revealed a potential correlation between structural stability and enzyme activity. When PsCDH was added to a multienzyme synergistic straw degradation system, the cellulose degradation rate increased by 1.84-fold. Moreover, mutant T1 further increased the degradation of lignocellulose in the mixed system. This study provides efficient enzyme sources and modification strategies for the high-efficiency biological conversion of straw and unconventional feedstock degradation, thereby possessing significant academic value and application prospects.

Unraveling the molecular mechanism of FgGcn5 inhibition by phenazine-1-carboxamide: combined in silico and in vitro studies.

Fusarium head blight (FHB), mainly caused by Fusarium graminearum (F. graminearum), remains a devastating disease worldwide. The histone acetyltransferase Gcn5 plays a crucial role in epigenetic regulation. Aberrant Gcn5 acetylation activity can result in serious impacts such as impaired growth and development in organisms. The secondary metabolite phenazine-1-carboxamide (PCN) inhibits F. graminearum by blocking the acetylation process of Gcn5 (FgGcn5), and is currently used to control FHB. However, the molecular basis of acetylation inhibition by PCN remains to be further explored. Our molecular dynamics simulations revealed that PCN binds to the cleft in FgGcn5 where histone H3 is bound, with key amino acid residues including Leu96 (L96), Arg121 (R121), Phe133 (F133), Tyr169 (Y169), and Tyr201 (Y201), preventing FgGcn5 from binding to histone H3 and affecting histone H3 from being acetylated. Experimental validation of key amino acid mutations further confirmed the impact of these mutations on the interaction of FgGcn5 with PCN and histone H3 peptide. In summary, our study sheds light on the mechanism by which PCN inhibits the acetylation function of FgGcn5, providing a foundation for the development of drugs or fungicides targeting histone acetyltransferases. © 2024 Society of Chemical Industry.

The oligonucleotides containing N7-regioisomer of guanosine. Influence on thermodynamic properties and structure of RNA duplexes.

During chemical synthesis of the purine riboside, the N7-regioisomer is kinetically formed whereas the N9-regioisomer is a thermodynamically formed product. We have studied the effect of substituting the N9-regioisomer of guanosine with its N7-regioisomer (N7-guanosine, 7G) at a central position of several RNA duplexes. We found that this single substitution by 7G severely diminished their thermodynamic stabilities when 7G paired with C and U, but remarkably, led to a significant amount of stabilization in most of the duplexes when forming mismatches with G and A. The extent of stabilization was observed to be dependent on the sequence and orientation of neighboring base pairs of N7-guanosine. 1D and 2D NMR studies on the duplexes along with extensive molecular dynamics simulations revealed the conformational differences occurring due to substitution of G by 7G and it was observed that the thermodynamic results were largely explainable by considering the formation of stable non-canonical hydrogen bonding interactions, although other interactions such as stacking and electrostatic interactions could also play a role. These observations can have important applications in the design of RNA-based disease diagnostics and therapeutics.

Hollow glass microsphere/polybutadiene composites with low dielectric constant and ultralow dielectric loss in high‐frequency

AbstractHigh‐frequency dielectric materials have been widely and rapidly applied in areas such as automotive radar, Internet of Things, artificial intelligence, and quantum computing. Currently, the challenge in high‐frequency dielectric materials lies in reducing the dielectric constant (Dk) and dielectric loss (Df) without sacrificing its mechanical properties. This study addresses this challenge by introducing air, as the most common “low dielectric factor,” into the polymer matrix in the form of hollow glass microspheres. Meanwhile, the reactive vinyl groups were also introduced onto the surface of the hollow glass microspheres, enabling an interfacial chemical reaction between the side vinyl groups of polybutadiene and its surface so that the organic–inorganic interface compatibility and interface peel strength are simultaneously improved. Consequently, the minimum Dk of 1.29 and Df of 0.0012 in 3–18 GHz are achieved, and the interface peel strength also reaches 0.65 N/mm. Molecular dynamics simulations, analysis of dielectric properties, and interface peel strength reveal the influence of hollow glass microspheres' morphology and chemical structure on their high‐frequency dielectric performance and adhesive strength. This paper provides effective strategies for the structural design and preparation of high‐frequency, low‐dielectric composites, contributing to the further development of next‐generation microwave communication devices towards higher frequencies and faster information transmission.

Scaffold Hopping Method for Design and Development of Potential Allosteric AKT Inhibitors.

Targeting AKT is a practical strategy for cancer therapy in many cancer types. Targeted inhibitors of AKT are attractive solutions for inhibiting the interconnected signaling pathways, like PI3K/Akt/mTOR. Allosteric inhibitors are more desirable among different classes of AKT inhibitors as they could be more specific with fewer off-target proteins. In this study, a ligand/structure-based pipeline was developed to design new allosteric AKT inhibitors by employing the core hopping method. Triciribine, a traditional allosteric AKT inhibitor was used as the template, and the FDA-approved kinase inhibitors for cancer treatment were considered as the cores. The allosteric site in the crystal structure of AKT1 was used to screen the designed compounds. The results were further evaluated using molecular docking, ADME/T analysis, molecular dynamics (MD) simulation, and binding free energy calculations. The outcomes introduced 24 newly designed inhibitors, amongst which three compounds C6, C20, and C16 showed remarkable binding affinity to AKT1. While the docking scores for triciribine was around -8.6 kcal/mol, the docking scores of these compounds were about -11 to -13 kcal/mol. The MD results indicated that designed compounds target the essential residues of the PH domain and kinase domain of AKT, such as Trp80, Thr211, Tyr272, Asp274, and Asp292. Scaffold hopping is a tremendous tool for designing novel anti-cancer agents by improving already known and potential drug compounds. The designed compounds are worth to be examined by experimental investigation in vitro and in vivo.

Molten-salt-mediated Chemical Looping Oxidative Dehydrogenation of Ethane with In-situ Carbon Capture and Utilization.

The molten-salt-mediated oxidative dehydrogenation (MM-ODH) of ethane (C2H6) via a chemical looping scheme represents an effective carbon capture and utilization (CCU) method for the valorization of ethane-rich shale gas and concurrent mitigation of carbon dioxide (CO2) emissions. Here, stepwise experimentation with Li2CO3-Na2CO3-K2CO3 (LNK) ternary salts (i) assessed how each component of the LNK mixture impacted ethane MM-ODH performance and (ii) explored physicochemical and thermodynamic mechanisms behind melt-induced changes to ethylene (C2H4) and carbon monoxide (CO) yields. Of fifteen screened LNK compositions, nine exhibited ethylene yields greater than 50% at 800°C while maintaining C2H4 selectivities of 85% or higher. LNK salts rich in Li2CO3 content yielded more ethylene and CO on average than their counterparts, and net CO2 capture per cycle reached a maximum of ~75%. Extended MM-ODH cycling also demonstrated long-term stability of a high-performing LNK medium. Density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations suggested that the molten salt does not directly activate C2H6. Meanwhile, an empirical model informed by experimental data and reaction thermodynamics adequately predicted overall MM-ODH performance from LNK composition and provided insights into the system's primary drivers.

PIM-1L Kinase Binds to and Inactivates SRPK1: A Biochemical and Molecular Dynamics Study.

SR/RS dipeptide repeats vary in both length and position, and are phosphorylated by SR protein kinases (SRPKs). PIM-1L, the long isoform of PIM-1 kinase, the splicing of which has been implicated in acute myeloid leukemia, contains a domain that consists largely of repeating SR/RS and SH/HS dipeptides (SR/SH-rich). In order to extend our knowledge on the specificity and cellular functions of SRPK1, here we investigate whether PIM-1L could act as substrate of SRPK1 by a combination of biochemical and computational approaches. Our biochemical data showed that the SR/SH-rich domain of PIM-1L was able to associate with SRPK1, yet it could not act as a substrate but, instead, inactivated the kinase. In line with our biochemical data, molecular modeling followed by a microsecond-scale all-atom molecular dynamics (MD) simulation suggests that the SR/SH-rich domain acts as a pseudo-docking peptide that binds to the same acidic docking-groove used in other SRPK1 interactions and induces inactive SRPK1 conformations. Comparative community network analysis of the MD trajectories, unraveled the dynamic architecture of apo SRPK1 and notable alterations of allosteric communications upon PIM-1L peptide binding. This analysis also allowed us to identify key SRPK1 residues, including unique ones, with a pivotal role in mediating allosteric signal propagation within the kinase core. Interestingly, most of the identified amino acids correspond to cancer-associated amino acid changes, validating our results. In total, this work provides insights not only on the details of SRPK1 inhibition by the PIM-1L SR/SH-domain, but also contributes to an in-depth understanding of SRPK1 regulation.

Anti-Inflammatory Humulene-Type Sesquiterpenoids from Asteriscus Graveolens

Objectives: Inflammation is the initial physiological reaction of the immune system to infection or irritation, leading significant risk factors for several forms of cancer. The genus Asteriscus has been observed to possess a notable abundance of sesquiterpenes with anti-inflammatory properties. This study was designed to assess the anti-inflammatory activity of the sesquiterpenoids isolated from Asteriscus graveolens. Methods: The organic extract of the Asteraceae plant A. graveolens was subjected to different chromatographic and spectroscopic techniques for isolation, purification, and identification of sesquiterpenoid contents. The isolated compounds were screened for anti-inflammatory activities in two animal models: rat paw edema and rat ear edema. Histopathological examinations as well as biochemical markers of inflammation were assessed. This was followed by in silico screening for anti-inflammatory activity. Results: Four known sesquiterpenoids were isolated from A. graveolens, including two humulene derivatives, namely, 9-oxohumula-4-en-6,15-olide (1), and 9-oxohumula-1(10)(Z),4,7(E)-trien-6,15-olide (2) and two bisabolene derivatives, identified as bisabola-2,10-dien-1-one (3) and 6- hydroxybisabola-2,10-dien-1-one (4) described. In the rat paw edema model, compound 2 showed highest activity in preventing formation carrageenan-induced paw edema. This was confirmed by histopathological examinations that indicated partial preservation of the epidermal and dermal layers. Further, the compound significantly inhibited cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) release. In the croton oil indued rat ear edema, compounds 2 and 4 significantly inhibited ear edema and protected against histopathological alterations. This was associated with prevention of myeloperoxidase (MPO) concentration in ear tissues. Molecular docking and molecular dynamic simulation indicated the affinity and docking stability of compounds 1-4 to the selected inflammatory protein. Conclusion: Phytochemical investigation of A. graveolens resulted in the isolation and characterization of four sesquiterpenes. In particular, compound 2 showed potent anti-inflammatory activity in carrageenan rat paw edema and croton oil ear edema.

Pangenome analysis of five representative Tropheryma whipplei strains following multiepitope-based vaccine design via immunoinformatic approaches.

Whipple disease caused by Tropheryma whipplei a gram-positive bacterium is a systemic disorder that impacts not only the gastrointestinal tract but also the vascular system, joints, central nervous system, and cardiovascular system. Due to the lack of an approved vaccine, this study aimed to utilize immunoinformatic approaches to design multiepitope -based vaccine by utilizing the proteomes of five representative T. whipplei strains. The genomes initially comprised a total of 4,844 proteins ranging from 956 to 1012 proteins per strain. We collected 829 nonredundant lists of core proteins, that were shared among all the strains. Following subtractive proteomics, one extracellular protein, WP_033800108.1, a WhiB family transcriptional regulator, was selected for the chimeric-based multiepitope vaccine. Five immunodominant epitopes were retrieved from the WhiB family transcriptional regulator protein, indicating MHC-I and MHC-II with a global population coverage of 70.61%. The strong binding affinity, high solubility, nontoxicity, nonallergenic properties and high antigenicity scores make the selected epitopes more appropriate. Integration of the epitopes into a chimeric vaccine was carried out by applying appropriate adjuvant molecules and linkers, leading to the vaccine construct having enhanced immunogenicity and successfully eliciting both innate and adaptive immune responses. Moreover, the abilityof the vaccine to bind TLR4, a core innate immune receptor, was confirmed. Molecular dynamics simulations have also revealed the promising potential stability of the designed vaccine at 400 ns. In summary, we have designed a potential vaccine construct that has the ability not only to induce targeted immunogenicity for one strain but also for global T. whipplei strains. This study proposes a potential universal vaccine, reducing Whipple's disease risk and laying the groundwork for future research on multi-strain pathogens.

Effect of Nanostructure and Crosslinks on Impact Resistance of Carbon Nanotube Films Under Micro-Ballistic Impact.

Carbon nanotube (CNT) films show great promise as an advanced bulletproof materials due to their excellent energy dissipation ability under impact loadings. However, it is challenging to determine the optimized architecture structure of CNTs to enhance the impact resistance of CNT films. In this study, the impact behavior of CNT films with various architecture structures werestudied by micro-ballistic impact experiments and coarse-grained molecular dynamics (CGMD) simulations. The micro-ballistic impact experimental results showed that the cross-ply laminated (CPL) structure enhances significantly the specific energy absorption (SEA) of CNT films compared to that with disordered structure due to the synergistic interactions between covalent bonds in CNT chains. On this basis, four CPL-CNT (CCNT) films with the same areal density (ρ2D) but different single-layer areal density ( ) and one disordered CNT (DCNT) film with the same ρ2D as the CCNT films wereconstructed in CGMD models. The simulation results showed that the SEAs of all the four CCNT films are higher than DCNT film, which is consistent with experiments. In addition, the SEAs of CCNT films increase with decreasing . However, too small can lead to local plugging failure of the CNT film and therefore decrease SEA of the CNT film. Moreover, adding crosslinks could further increase the SEAs of both the DCNT and the CCNT films due to the strengthened interactions of adjacent CNTs. The crosslinked CCNT films with appropriate ρ2D is still much higher than the crosslinked DCNT films. Furthermore, it wasfurther found that when the strength of the crosslinks aligns with that of the CNT beads, the CNT film achieves preeminent impact resistance. This study provides a pathway for enhancing the impact resistance of CNT films by optimizing the microstructure and introducing crosslinks betweenCNTs.

The Effects of Inhibitor Chivosazole A on Actin Interacting with Profilin: A Theoretical Study

AbstractActin is highly conserved and contributes to numerous cellular activities. Profilin, one of actin binding proteins, promotes the exchange rate of nucleotide of actin, which leads to a fast elongation of actin filament. To slow down the elongation of filament, chivosazole A (ChivoA) is developed as an inhibitor of blocking actin‐profilin interaction. Intriguingly, known from the solved crystal structure, ChivoA does not bind on the interface between actin and profilin. Here, molecular dynamics (MD) simulation is used to study the possible mechanism how ChivoA inhibits actin‐profilin interaction. First, principal component analysis and representative structures comparisons reveal that the conformation of ChivoA‐bound actin is restrained at a closed state, whereas a trend toward an open state is found in profilin‐bound actin. Then, Peptide Gaussian accelerated MD shows that ChivoA limits the ability of the DNase I binding loop (D‐loop) swings and enlarges a distance between two major profilin binding regions. On the contrary, the distance between these two regions of profilin‐bound actin decreases in a clamp‐like motion mode. Finally, binding energies are calculated by molecular mechanics/poisson‐boltzmann surface area method and display that the ChivoA‐bound actin is less favorable for profilin binding.