Oil/water interface behavior of hesperidin methylchalcone and its application in nano-emulsions.

The behavior of hesperidin methylchalcone (HMC) at the oil/water interface was examined through experimental and molecular simulation methods, and a nano-emulsions based on HMC was subsequently fabricated. The findings indicated that HMC spontaneously aggregated at the oil-water interface, leading to a reduction in interfacial tension and an increase in interfacial thickness. Furthermore, its glycoside and benzene ring showed tendencies to interact with water and medium-chain triglyceride, respectively. The HMC addition amount (w), homogenization times (n) and homogenization pressure (p) significantly influenced the formation of the nano-emulsions. The nano-emulsion with an oil-droplet size of 277.26 ± 13.62 nm was obtained at w = 1.0 %, p = 200 bar, and n = 6. When compared to the Tween 20 nano-emulsion, the HMC nano-emulsion demonstrated superior storage stability, antioxidant activity, and lutein bioaccessibility. It could achieve the slow release of HMC. These findings not only broaden the application range of HMC but also contribute to the advancement of functional nano-emulsions.

The hemostatic molecular mechanism of Sanguisorbae Radix's pharmacological active components based on HSA: Spectroscopic investigations, molecular docking and dynamics simulation.

The interactions between human serum albumin (HSA) and the hemostatic components of the Chinese medicine Sanguisorbae Radix (SR), specifically phenolic acid compounds such as caffeic acid (CA), ferulic acid (FA) and their 1:1 mixture (1:1) were studied to investigate the molecular mechanism underlying the hemostatic effect of SR. Network pharmacology combined with the experimental and computational data revealed that HSA is one of the hemostatic targets to SR phenolic acids. SDS-PAGE and multi-spectroscopy demonstrated that the phenolic acids bind to the Sudlow site I on HSA, altering its structure and influencing its migration velocity. There is an observed synergistic effect upon the mixture of CA and FA. Quantum chemistry, molecular docking, and molecular dynamics simulations indicate that the binding of phenolic acids to HSA is stable, and variations in binding efficiency are associated with the hydrophobicity of the substituent at the C3 position of the side chain, and also, the key amino acids and functional groups for hemostasis of SR were identified, along with the active sites that contribute to the synergistic enhancement by phenolic acids.

Self-Assembled PEGylated Nanocubes Based on Hydrophobic Camptothecin and Doxorubicin for Combinational Therapy of Colorectal Cancer.

Nanoassemblies based on drug conjugates with high drug loading efficiency and stability have been regarded as promising candidates for the next generation of drug formulations. However, they are mostly amphiphilic. Here, a dual-hydrophobic drug conjugate-based nanoassembly has been created for enhanced synergistic antiproliferation against colorectal cancer cells. Camptothecin (CPT) and doxorubicin (DOX) were chosen as the hydrophobic drugs and covalently linked with a disulfide bond (-ss-). The synthesized CPT-ss-DOX can self-assemble into nanocubes (NCs) in an aqueous solution with the assistance of a small amount of polyethylene glycol (PEG), named PEGylated CPT-ss-DOX NCs. The PEGylated CPT-ss-DOX NCs were approximately 111.8 nm, possessing a crystal structure and a very low critical aggregation concentration (8.36 µg·mL-1). The self-assembly mechanism was studied using molecular docking and molecular dynamic simulation methods. The NCs demonstrated excellent storage stability and improved water solubility of CPT and DOX. These NCs could be taken up by cancer cells and gradually release the drugs. In addition, they had higher toxicity to cancer cells than a mixture of CPT and DOX, while they displayed reduced toxicity to normal cells. Due to assembly and PEG modification, the NCs improved drug retention time and enhanced accumulation at the tumor site. More importantly, they significantly inhibited colorectal tumor growth (58.37%) in vivo, superior to the CPT+DOX mix (42.63%). Moreover, the NCs reduced the cardiac toxicity of free drugs. Therefore, the prepared PEGylated CPT-ss-DOX NCs hold great potential for clinical transformation and provide a novel method for the self-delivery of hydrophobic molecules in cancer therapy.

Molecular Simulation Analysis of Polyurethane Molecular Structure under External Electric Field.

Polyurethane (PU) materials are extensively utilized in power equipment. This paper introduces a comprehensive evaluation method that combines electromagnetics and computational chemistry based on the Density Functional Theory (DFT) to elucidate the impact of external electric fields on the molecular structure of PU during electrical contact. The study focuses on the microstructural and molecular energy changes in the hard (HS) and soft (SS) segments of PU under the influence of an electric field of uniform intensity. Findings indicate that the total energy of HS molecules decreases markedly as the electric field intensity increases, accompanied by a significant rise in both the dipole moment and polarizability. Conversely, the total energy and polarizability of the SS molecules decrease, while the dipole moment experiences a slight increase. Under the influence of a strong electric field, HS molecules tend to stretch towards the extremities of the main chain, leading to structural instability and the cleavage of hydroxyl O-H bonds. Meanwhile, the carbon chain of the SS molecules twists towards the center under the electric field, with no chemical bond rupture observed. At an electric field intensity of 8.227 V/nm, the HOMO-LUMO gap of the HS molecule narrows sharply, signifying a rapid decline in the molecular structure stability, corroborated by infrared spectroscopy analysis. These findings offer theoretical insights and guidance for the modification of PU materials in power equipment applications.

Comprehensive Investigation into the Impact of Degradation of Recycled Polyethylene and Recycled Polypropylene on the Thermo-Mechanical Characteristics and Thermal Stability of Blends.

The impact of degradation on plastics is a critical factor influencing their properties and behavior, particularly evident in polyethylene (PE) and polypropylene (PP) and their blends. However, the effect of photoaging and thermal degradation, specifically within recycled polyethylene (rPE) and recycled polypropylene (rPP), on the thermo-mechanical and thermostability aspects of these blends remains unexplored. To address this gap, a range of materials, including virgin polyethylene (vPE), recycled polyethylene (rPE), virgin polypropylene (vPP), recycled polypropylene (rPP), and their blends with different ratios, were comprehensively investigated. Through a systematic assessment encompassing variables such as melting flow index (MFI), functional groups, mechanical traits, crystallization behavior, microscopic morphology, and thermostability, it was found that thermo-oxidative degradation generated hydroxyl and carboxyl functional groups in rPE and rPP. Optimal mechanical properties were achieved with a 6:4 mass ratio of rPE to rPP, as validated by FTIR spectroscopy and microscopic morphology. By establishing the chemical model, the changes in the system with an rPE-rPP ratio of 6:4 and 8:2 were monitored by the molecular simulation method. When the rPE-rPP ratio was 6:4, the system's energy was lower, and the number of hydrogen bonds was higher, which also confirmed the above experimental results. Differential scanning calorimetry revealed an increased crystallization temperature in rPE, a reduced crystallization peak area in rPP, and a diminished crystallization capacity in rPE/rPP blends, with rPP exerting a pronounced influence. This study plays a pivotal role in enhancing recycling efficiency and reducing production costs for waste plastics, especially rPE and rPP-the primary components of plastic waste. By uncovering insights into the degradation effects and material behaviors, our research offers practical pathways for more sustainable waste management. This approach facilitates the optimal utilization of the respective performance characteristics of rPE and rPP, enabling the development of highly cost-effective rPE/rPP blend materials and promoting the efficient reuse of waste materials.

Molecular Simulation of the Water Diffusion Behavior and Electronic Properties of Boron-Nitride-Composited Mineral Oil.

Despite the fact that doping nanoparticles into insulating transformer oil has proven to be an effective method of enhancing its dielectric and electrical properties, it remains unclear how different types and surface conditions of nanoparticles may affect their dielectric and electrical properties. Therefore, the effect of doping various types of BN nanoparticles (nanosphere, nanotube, and nanosheet) in insulating mineral oil (MO) on the diffusion properties of water molecules and electrical properties across the BN/MO interface was investigated using molecular dynamics (MD) and Density Functional Theory (DFT) simulations. Our results show that different surface morphology and grafted functional groups in different types of BN nanoparticles have a significant impact both on the water diffusion behavior and the interfacial potential barrier across the interface between BN and MO. In the MO system directly doped by BN nanospheres, water diffusion behavior is not significantly restricted. However, grafting -NH2 polar groups onto the BN nanoparticle surface may significantly limit the diffusion behavior of water due to the strong attraction between the -NH2 polar groups and water molecules; the most significant effect is with nanospheres, followed by nanotubes and nanosheets. In terms of electrical properties across the interface between BN and MO, the h-BN surface (derived from BN nanosheets and nanotubes) acts as a trap for electrons in MO (-0.59 eV), while the c-BN surface (derived from BN nanospheres) acts as a potential barrier for electrons in MO (1.45 eV), and it is noteworthy that the presence of water molecules near the interface between BN and MO has little impact on the potential barriers. Advancing a fundamental understanding of the electrical and water diffusion properties of MO in correlation with the surface morphology of different types of nanoparticles is key to improving the insulation properties of oil-impregnated power transformers.

The molecular mechanisms of TRß receptor interaction with polychlorinated biphenyls: A multispectral and computational exploration.

The thyroid hormone (TH) system is susceptible to the toxic effects of polychlorinated biphenyls (PCBs). Pollutants may disrupt the TH system by binding to serum TH transport proteins or interacting with thyroid hormone receptors (TRs) in target cells. However, the molecular mechanism of interaction with the Thyroid Hormone Receptor Beta (TRß) is not fully understood. This study employed fluorescence, UV-visible absorption, three-dimensional fluorescence, and Fourier-transform infrared spectroscopy, along with molecular docking and molecular dynamics simulations, to investigate the interaction between TRß and PCBs. Moreover, molecular docking and fluorescence resonance energy transfer (FRET) findings suggest that TRß and PCBs underwent resonance energy transfer consistent with Förster's theory. The root mean square deviation (RMSD) and docking outcomes indicate that the TRß-PCB29 complex exhibited optimal structural stability. Thus, the study concludes that integrating spectroscopic data with molecular docking is essential for a comprehensive analysis. Further analysis of intermolecular interactions using quantum chemistry and reduced density gradient analysis (RDG) analysis revealed that van der Waals forces are the primary drivers of PCBs to TRß.

Crystallization and intermolecular hydrogen bonding in carbamazepine-polyvinyl pyrrolidone solid dispersions: An experiment and molecular simulation study on drug content variation.

The choice of drug content is a critical factor as far as the solid dispersion is concerned. This investigation aims to build the relationship between the drug content, intermolecular hydrogen bonding and the crystalline of the carbamazepine-polyvinyl pyrrolidone solid dispersion. In this work, the microstructural changes of solid dispersions were investigated using experimental characterization combined with molecular simulation. Experimental investigations demonstrated that increasing the drug content enhances the intermolecular hydrogen bonding between drugs, resulting in the crystalline phase of the drug emerged in the solid dispersion. This negatively affects the solubility and stability of solid dispersions. Molecular simulations were then used to analyze the changes of intermolecular hydrogen bonding at different drug content in the system. It revealed a tenfold increase in drug-drug hydrogen bonding concentration as drug content elevated from 10% to 50%, while the drug-excipient hydrogen bonding concentration decreased by 45%. The correlation analysis proves the significant relationships among the drug content, intermolecular hydrogen bonding, and crystallinity of solid dispersion. Using polynomial fitting analysis, the quantitative relationships between the drug content and crystalline properties were investigated. This study will offer valuable insights into the impact of drug content on the performance of solid dispersion.

Differentiated adsorption of acetaminophen and diclofenac via alkyl chain-modified quaternized SBA-15: insights from molecular simulation.

The increasing presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems pose significant environmental concerns. This study addresses this issue by synthesizing quaternized mesoporous SBA-15 (QSBA) with varied alkyl chain lengths of C1QSBA, C8QSBA, and C18QSBA. QSBA utilizes dual mechanisms: hydrophobic interactions via the alkyl chain and electrostatic attraction/ion exchange via the ammonium group. Diclofenac (DCF) and acetaminophen (ACT) were selected as target PPCPs due to their contrasting dissociation properties and hydrophobicity, which are the main characteristics of PPCPs. The adsorption of DCF and ACT revealed that longer alkyl chains enhanced the adsorption capacity of ACT through hydrophobic interactions, whereas dissociated DCF (DCF-) adsorption was superior owing to its high hydrophobicity (log Kow = 4.5) and electrostatic attraction. pH levels between 6 and 8 resulted in a high affinity for DCF-. Notably, among the three alkyl chains, only C18QSBA exhibited the most effective adsorption for DCF-. These PPCPs adsorption trends were confirmed through molecular simulations of adsorption under conditions in which competing ions coexisted. The molecular simulations show that while DCF- has lower adsorption energy than Cl-, OH-, and H3O+ ions in QSBA, enhancing its adsorption under various pH conditions. Conversely, ACT exhibits a higher adsorption energy, which reduces its adsorption efficiency. This suggests the potential application of QSBA with long alkyl chains in the treatment of highly hydrophobic and negatively charged PPCPs. Furthermore, this study emphasizes the importance of simulating adsorption under competing ion conditions.

Adsorption/desorption characteristics of methane on moist shale under high temperature and pressure: an experimental and molecular simulation study.

The adsorption/desorption characteristics of methane (CH4) on moist shale are of great significance for shale gas exploration and production. However, the influence of moisture on CH4 adsorption/desorption under high temperature and pressure conditions, which is consistent to shale reservoirs (burial depths about 3500-4500 m) in China, remained unclear. In this study, quantitative analysis toward moisture dependence of CH4 adsorption/desorption capability on shales was investigated through experimentation and molecular dynamics simulation under moisture contents of 0%, 0.204%, 0.445%, 0.677%, and 0.965%. Results show that with increasing moisture content, the isothermal adsorption capacity of CH4 decrease, and it reaches 36.80% and 10.00% at moisture content of 0.965% in experimentation and simulation, respectively. Simultaneously, the hysteresis index of CH4 desorption increase by 19.64% and 4.52%. The role of water molecules hindering CH4 desorption under low and high moisture content was clarified. At low moisture content, water molecules are mainly adsorbed on the pore walls, thereby reducing the size of the pore throat and hindering CH4 transport pathways. At high moisture content, many water molecules escape from the original adsorption sites and form clusters in the middle of the pores, blocking the pore throats. Meanwhile, CH4 is re-adsorbed onto the exposed adsorption sites of water, which leads to CH4 desorption hysteresis. The results provide valuable insights for shale gas exploration and production under practical water-bearing shale reservoir conditions.

Structural changes of wheat starch and activity inhibition of α-glucosidase by persimmon (Diospyros kaki Thunb.) leaves extract retarding starch digestibility.

Elevated blood sugar levels caused by starch digestion was a target for controlling diabetes mellitus. The in vitro and in vivo digestibility of wheat starch was evaluated to find that adding 15 % persimmon leaf extract (PLE) to starch reduced its digestibility by 69.50 % and the peak postprandial blood glucose by 23.63 %. Subsequently, we observed under scanning electron microscopy and atomic force microscopy that the presence of PLE led to the destruction of starch structure and the aggregation of α-glucosidase so as to decrease starch digestion and hinder the binding of starch to α-glucosidase. Through multi-spectral analysis, PLE hindered the clathrate of iodine and starch, and also increased the crystallinity of starch by 48.58 %. For α-glucosidase inhibitory activity (IC50 = 72.49 µg/mL), PLE preferentially occupied the active center of α-glucosidase, changed its fluorescence characteristics and secondary structure through hydrogen bonding and hydrophobic interaction. Moreover, among the 23 potential α-glucosidase inhibitors screened from PLE, combined with molecular simulation, Procyanidin B2 had the strongest inhibitory effect (IC50 = 33.22 µg/mL) and binding energy (-7.09 kcal/mol), which was most effectively inhibitory on digestion. These results indicated the potential of PLE in hypoglycemia targeting both starch and α-glucosidase.

Polymyxin B1 in the E. coli inner membrane: a complex story of protein and lipopolysaccharide mediated insertion.

The rise in multi-drug resistant Gram-negative bacterial infections has led to an increased need for 'last-resort' antibiotics such as polymyxins. However, the emergence of polymyxin-resistant strains threatens to bring about a post-antibiotic era. Thus, there is a need to develop new polymyxin-based antibiotics, but a lack of knowledge of the mechanism of action of polymyxins hinders such efforts. It has recently been suggested that polymyxins induce cell lysis of the Gram-negative bacterial inner membrane (IM) by targeting trace amounts of lipopolysaccharide (LPS) localized there. We use multiscale molecular dynamics (MD) including long-timescale coarse-grained (CG) and all-atom (AA) simulations to investigate the interactions of polymyxin B1 (PMB1) with bacterial IM models containing phospholipids (PLs), small quantities of LPS, and IM proteins. LPS was observed to (transiently) phase separate from PLs at multiple LPS concentrations, and associate with proteins in the IM. PMB1 spontaneously inserted into the IM and localized at the LPS-PL interface, where it cross-linked lipid headgroups via hydrogen bonds, sampling a wide range of interfacial environments. In the presence of membrane proteins, a small number of PMB1 molecules formed interactions with them, in a manner that was modulated by local LPS molecules. Electroporation-driven translocation of PMB1 via water-filled pores was favored at the protein-PL interface, supporting the 'destabilizing' role proteins may have within the IM. Overall, this in-depth characterization of PMB1 modes of interaction reveals how small amounts of mislocalized LPS may play a role in pre-lytic targeting and provides insights that may facilitate rational improvement of polymyxin-based antibiotics.

New insight into synergistic interaction between the backbone or side chain of xanthan gum and the backbone of Gleditsia sinensis polysaccharide.

In this study, the synergistic effect and weak gel mechanism of XG and Gleditsia sinensis polysaccharide (GSP) in different ratios were studied through the rheological properties, microstructure and molecular simulation based on density functional theory (DFT). The results of rheological properties showed that the mixtures formed a weak gel at the concentration of 0.5 % (w/v), with the synergistic impact peaking at a XG/GSP ratio of 3:7. Weak gels produced by XG and GSP had the intersection of G' and G" within the temperature sweep range, and the largest change in the G' slope at a XG/GSP ratio of 3:7. By calculating the interaction energy, it was found that the backbone of XG was more likely to interact with the backbone of GSP. Furthermore, the XG mainchain intersected with the backbone of GSP in a cross shape ("X" shape). As a result, this paper proposed a possible mechanism for the formation of the XG/GSP weak gel, with XG as the main chain and GSP as the grid point, and the main interaction type being hydrogen bonding, with the van der Waals force also involved. The results provide new insight for designing and producing physical gels with specific interactions in food industry.

Unraveling the molecular basis for effective regulation of integrin α5ß1 for enhanced therapeutic interventions.

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5ß1 is a heterodimer of α5 and ß1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5ß1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5ß1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5ß1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5ß1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5ß1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5ß1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5ß1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5ß1.

Integrative experimental and computational analysis of the impact of KGM's polymerization degree on wheat starch's pasting and retrogradation characteristics.

This study investigated the influence of Konjac Glucomannan (KGM) with varying degrees of polymerization (DKGMx) on the gelatinization and retrogradation characteristics of wheat starch, providing new insights into starch-polysaccharide interactions. This research uniquely focuses on the effects of DKGMx, utilizing multidisciplinary approaches including Rapid Visco Analysis (RVA), Differential Scanning Calorimetry (DSC), rheological testing, Low-Field Nuclear Magnetic Resonance (LF-NMR), and molecular simulations to assess the effects of DKGMx on gelatinization temperature, viscosity, structural changes post-retrogradation, and molecular interactions. Our findings revealed that higher degrees of polymerization (DP) of DKGMx significantly enhanced starch's pasting viscosity and stability, whereas lower DP reduced viscosity and interfered with retrogradation. High DP DKGMx promoted retrogradation by modifying moisture distribution. Molecular simulations revealed the interplay between low DP DKGMx and starch molecules. These interactions, characterized by increased hydrogen bonds and tighter binding to more starch chains, inhibited starch molecular rearrangement. Specifically, low DP DKGMx established a dense hydrogen bond network with starch, significantly restricting molecular mobility and rearrangement. This study provides new insights into the role of the DP of DKGMx in modulating wheat starch's properties, offering valuable implications for the functional improvement of starch-based foods and advancing starch science.

Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE.

Small-molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures. Moreover, designing selective drugs often benefits from the targeting of diverse metastable conformations. Therefore, direct application of AlphaFold2 models in virtual screening and drug discovery remains tentative. Here, we demonstrate an AlphaFold2-based framework combined with all-atom enhanced sampling molecular dynamics and Induced Fit docking, named AF2RAVE-Glide, to conduct computational model-based small-molecule binding of metastable protein kinase conformations, initiated from protein sequences. We demonstrate the AF2RAVE-Glide workflow on three different mammalian protein kinases and their type I and II inhibitors, with special emphasis on binding of known type II kinase inhibitors which target the metastable classical DFG-out state. These states are not easy to sample from AlphaFold2. Here, we demonstrate how with AF2RAVE these metastable conformations can be sampled for different kinases with high enough accuracy to enable subsequent docking of known type II kinase inhibitors with more than 50% success rates across docking calculations. We believe the protocol should be deployable for other kinases and more proteins generally.

Effect of chitooligosaccharide on the binding domain of the SARS-COV-2 receptor.

The receptor-binding domain (RBD) is crucial for understanding how severe acute respiratory syndrome coronavirus (SARS-CoV-2) recognizes and infects host cells. Chitooligosaccharide (CS) exhibits diverse antiviral activities, with its derivatives showing remarkable efficacy in blocking SARS-CoV-2 infection. Thus, this study employed spectroscopy, virus-infected cell experiments, and molecular simulation to investigate the molecular interactions between CS and SARS-CoV-2 RBD, as well as their mechanisms. In spectroscopic experiments, all four CS variants with different molecular weights formed interactions with the RBD. These variants increased the resistance of HEK293ACE2 cells to SARS-CoV-2 invasion. Molecular docking revealed that the four CS variants could bind to the RBD through hydrogen bonding or salt-bridge interactions, forming stable complexes. Chitotetraose provided stronger protection to HEK293ACE2 cells compared to other CS variants and displayed higher molecular docking scores. Further investigation into the optimal docking conformation of chitotetraose was conducted through molecular dynamics simulation methods. This study lays a solid theoretical foundation and provides a scientific basis for the development of targeted RBD inhibitors, as well as drug screening and application against novel coronaviruses.

Hypoglycaemic activity of the anthocyanin enriched fraction of Lycium ruthenicum Murr. Fruits and its ingredient identification via UPLC-triple-TOF-MS/MS.

Lycium ruthenicum Murr. is mainly distributed in the northwest region of China and its berries are rich in anthocyanin. This study evaluated the hypoglycaemic activity of the anthocyanin-enriched fraction (AEF) of L. ruthenicum Murr. on α-glucosidase in vivo and in vitro. Overall, 10 anthocyanins were identified via UPLC-Triple-TOF-MS/MS. The AEF exhibited strong inhibitory activity against α-glucosidase, with an IC50 value of 4.468 mg/mL. It behaved as a reversible, mixed-type inhibitor. Molecular docking and dynamic results indicated that the compounds in AEF interacted with enzymes primarily through van der Waals and hydrogen bond and the complex system was stable. The postprandial blood glucose and area under the curve of diabetic mice was significantly decreased by AEF in the carbohydrate tolerance experiments. The results indicate that the AEF from L. ruthenicum Murr. berries could be as a promising food supplement for managing blood sugar levels in patients with diabetes mellitus.

Integrated structural proteomics and machine learning-guided mapping of a highly protective precision vaccine against mycoplasma pulmonis.

Mycoplasma pulmonis (M. pulmonis) is an emerging respiratory infection commonly linked to prostate cancer, and it is classified under the group of mycoplasmas. Improved management of mycoplasma infections is essential due to the frequent ineffectiveness of current antibiotic treatments in completely eliminating these pathogens from the host. The objective of this study is to design and construct effective and protective vaccines guided by structural proteomics and machine learning algorithms to provide protection against the M. pulmonis infection. Through a thorough examination of the entire proteome of M. pulmonis, four specific targets Membrane protein P80, Lipoprotein, Uncharacterized protein and GGDEF domain-containing protein have been identified as appropriate for designing a vaccine. The proteins underwent mapping of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) (IFN)-γ ±, and B-cell epitopes using artificial and recurrent neural networks. The design involved the creation of mRNA and peptide-based vaccine, which consisted of 8 CTL epitopes associated by GGS linkers, 7 HTL (IFN-positive) epitopes, and 8 B-cell epitopes joined by GPGPG linkers. The vaccine designed exhibit antigenic behavior, non-allergenic qualities, and exceptional physicochemical attributes. Structural modeling revealed that correct folding is crucial for optimal functioning. The coupling of the MEVC and Toll-like Receptors (TLR)1, TLR2, and TLR6 was examined through molecular docking experiments. This was followed by molecular simulation investigations, which included binding free energy estimations. The results indicated that the dynamics of the interaction were stable, and the binding was strong. In silico cloning and optimization analysis revealed an optimized sequence with a GC content of 49.776 % and a CAI of 0.982. The immunological simulation results showed strong immune responses, with elevated levels of active and plasma B-cells, regulatory T-cells, HTL, and CTL in both IgM+IgG and secondary immune responses. The antigen was completely cleared by the 50th day. This study lays the foundation for creating a potent and secure vaccine candidate to combat the newly identified M. pulmonis infection in people.

Insilico assessment of hesperidin on SARS-CoV-2 main protease and RNA polymerase: Molecular docking and dynamics simulation approach.

The present study uses molecular docking and dynamic simulations to evaluate the inhibitory effect of flavonoid glycosides-based compounds on coronavirus Main protease (Mpro) and RNA polymerase. The Molegro Virtual Docker (MVD) software is utilized to simulate and calculate the binding parameters of compounds with coronavirus. The docking results show that the selected herbal compounds are more effective than those of chemical compounds. It is also revealed that five herbal ligands and two chemical ligands have the best docking scores. Furthermore, a Molecular Dynamics (MD) simulation was conducted for Hesperidin, confirming docking results. Analysis based on different parameters such as Root-mean-square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg), Solvent accessibility surface area (SASA), and the total number of hydrogen bonds suggests that Hesperidin formed a stable complex with Mpro. Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) analysis was performed to compare Hesperidin and Grazoprevir as potential antiviral medicines, evaluating both herbal and chemical ligand results. According to the study, herbal compounds could be effective on coronavirus and are admissible candidates for developing potential operative anti-viral medicines. Hesperidin was found to be the most acceptable interaction. Grazoprevir is an encouraging candidate for drug development and clinical trials, with the potential to become a highly effective Mpro inhibitor. Compared to RNA polymerase, Mpro showed a greater affinity for bonding with Hesperidin. van der Waals and electrostatic energies dominated, creating a stable Hesperidin-Mpro and Hesperidin-RNA polymerase complex.