Enzymatic Reaction Research Articles

Metal-ligand cross-link strategy engineered iron-doped dopamine-based superstructure as peroxidase-like nanozymes for detection of glucose.

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of beingeasy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000μM, and the limit of detection is 17.5μM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

Screening of enhanced biohydrogen production from anaerobic fermentation amended with nano-sized barium ferrite supported by aluminum oxide

Anaerobic fermentation has attracted wide attention to effectively reduce carbon footprint and alleviate potential energy shortages, which is being regarded as a sustainable and promising technology to obtain high biohydrogen production from widespread organic wastes. However, biohydrogen commercial uptake is now dominantly inhibited by the low hydrogen yield and process instability. In this work, Al2O3/BaFe2O4 nanoparticles (NPs) are successfully applied to anaerobic fermentation for investigating their effects on hydrogen yield, activity of bacteria and microbial community structure. The benefits of Al2O3/BaFe2O4 NPs with respect to microbial metabolism, reactivity of enzymes and process optimization are systematically researched through batch experiments. In addition, various characterizations are used to verify the physical and chemical properties of Al2O3/BaFe2O4 NPs. The results show that the activity of hydrogenases and microbe metabolism can be significantly inhibited by excess addition of Al2O3/BaFe2O4 NPs (150 mg/L and 200 mg/L) while the optimum addition 100 mg/L of Al2O3/BaFe2O4 NPs can boost the biohydrogen yield by 49% via facilitating microorganism growth and enhancing key enzymatic activities, which indicate that the Al2O3/BaFe2O4 NPs display a beneficial influence on electron transfer efficiency and process stability. The existence of Fe3+, Al3+and Ba2+ derived from the corrosion of Al2O3/BaFe2O4 NPs by organic acids synergistically improve the microbial transmembrane transportation and substrate utilization, which contribute to higher conversion rate of glucose into acetate, butyrate and H2. Meanwhile, the complementary functions of Fe3+ and Al3+ can powerfully shorten the lag phase and promote the glycolysis, which finally accelerate the dark fermentation process. Compared with the control group, Clostridium_sensu_stricto_1 is selectively enriched by the addition of Al2O3/BaFe2O4 NPs, which keep heavily involved in the synthesis of H2. On balance, this study provides an effective strategy to enhance hydrogen productivity and maintain process stability, which offer the valuable information for the sustainable utilization of sewage sludge.

Vitamin C: Is it Relevant or Obsolete in the Modern Era?

Abstract Purpose In this review, we discuss the historic background of vitamin C, vitamin C’s physiology, its dietary sources, and how deficiency can manifest. We also discuss modern studies investigating the role of Vitamin C in immunity, in cardiovascular disease, and in chronic conditions. Summary In the body, vitamin C acts as an essential cofactor in several enzymatic reactions including, but not limited to, neurotransmitter synthesis, hormone amidation, collagen synthesis, hypoxic transcription factor modification, and epigenetic modifications. Scurvy, caused by severe vitamin C deficiency, is an infamous disease recorded in historical documents, with patients presenting with joint ache, bleeding gums, depression, and hysteria. Since humans are unable to naturally synthesize ascorbic acid, they must rely on dietary sources such as fruits and vegetables in order to maintain their vitamin C levels and avoid such manifestations. Maintaining stable vitamin C levels remains increasingly important in the modern era, particularly for the vulnerable pediatric patient with chronic conditions or critical illness. Regulating vitamin C levels could decrease morbidity and mortality in the chronic and critically ill pediatric population. Moving forward, there is a need for more head-to-head trials pertaining to vitamin C’s role in improving immunity, modifying cardiovascular risk, and altering cancer prognosis.

Epigenetic and Gene Therapy in Human and Veterinary Medicine

Abstract Gene therapy is a focus of interest in both human and veterinary medicine, especially in recent years due to the potential applications of CRISPR/Cas9 technology. Another relatively new approach is that of epigenetic therapy, which involves an intervention based on epigenetic marks, including DNA methylation, histone post-translational modifications, and post-transcription modifications of distinct RNAs. The epigenome results from enzymatic reactions which regulate gene expression without altering DNA sequences. In contrast to conventional CRISP/Cas9 techniques, the recently established methodology of epigenetic editing mediated by the CRISPR/dCas9 system is designed to target specific genes without causing DNA breaks. Both natural epigenetic processes and epigenetic editing regulate gene expression and thereby contribute to maintaining the balance between physiological functions and pathophysiological states. From this perspective, knowledge of specific epigenetic marks has immense potential in both human and veterinary medicine. For instance, the use of epigenetic drugs (chemical compounds with therapeutic potential affecting the epigenome) seems to be promising for the treatment of cancer, metabolic, and infectious diseases. Also, there is evidence that an epigenetic diet (nutrition-like factors affecting epigenome) should be considered as part of a healthy lifestyle and could contribute to the prevention of pathophysiological processes. In summary, epigenetic-based approaches in human and veterinary medicine have increasing significance in targeting aberrant gene expression associated with various diseases. In this case, CRISPR/dCas9, epigenetic targeting, and some epigenetic nutrition factors could contribute to reversing an abnormal epigenetic landscape to a healthy physiological state.

Enzymatic Reaction Enhanced Diffusion Accelerates Cargo Transport through Micro/Nano-Channels.

Energy conversion and transfer of enzyme-catalyzed reactions at molecular level are an interesting and challenging scientific topic that helps understanding biological processes in nature. In this study, it is demonstrated that enzyme-catalyzed reactions can enhance diffusion of surrounding molecules and thus accelerate cargo transport within 1D micro/nanochannels. Specifically, urease is immobilized on the inner walls of silica micro/nano-tubes to construct bio-catalytically active micro/nanochannels. The catalytic reaction inside the channels drives a variety of cargoes, including small dye molecules, polymers, and rigid nanoparticles (e.g., quantum dots, QDs), to pass through these micro/nanochannels much faster than they will by free diffusion. The enhanced diffusion of molecular species inside the channels is validated by direct observation of the Brownian motion of tracer particles, and further confirmed by significantly enhanced Raman intensity of reporter molecules. Finite element and Brownian dynamics simulations provide a theoretical understanding of these experimental observations. Furthermore, the effect of the channels' size on the diffusion enhancement is examined. The acceleration effect of the cargo transport through these enzymatically active micro/nanochannels can be turned on or off via chemical activators or inhibitors. This study provides valuable insights on the design of biomimetic channels capable of controlled and efficient transmembrane transport.

Functional characterization of helminth-associated Clostridiales reveals covariates of Treg differentiation

BackgroundParasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura, display microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes with immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. In this study, we aimed to further characterize the functional properties of these bacteria.ResultsClostridiales isolates were profiled for their ability to perform 57 enzymatic reactions and produce short-chain fatty acids (SCFAs) and hydrogen sulfide, revealing that these bacteria were capable of a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T-cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching.ConclusionWe identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region.-EyM7p7tfAvrAjtAePB85JVideo

Enhancement of Catalytic Efficiency of Enzymatic Redox Reactions by Composing Horseradish Peroxidase-Modified Electrode with Ionic Liquids

We have kinetically estimated the enzymatic redox reaction at the horseradish peroxidase (HRP)-modified electrode combined with ionic liquids by adding N-(2-methoxythethyl)-N-methylpyrrolidinium bis(trifluoromethane sulfonyl)imide (MEMPTFSI) to HRP/carbon paste (CP)/Ketjenblack EC600JC (EC). The fluctuation of the steady-state reduction current of HRP at the HRP/CP-modified electrode progressively increased as the applied potential was lowered. The enzymatic redox reaction with hydrogen peroxide as a substrate at the HRP/CP/EC/MEMPTFSI-modified electrode and the HRP/CP-modified electrode could be correlated by the Michaelis–Menten equation. The Michaelis constant of the enzymatic redox reaction at the HRP/CP/EC/MEMPTFSI-modified electrode was the same as that at the HRP/CP-modified electrode. On the other hand, the turnover number of the enzymatic redox reaction at the HRP/CP/EC/MEMPTFSI-modified electrode was six times larger than that at the HRP/CP-modified electrode. Consequently, the specificity constant of the enzymatic redox reaction at the HRP/CP/EC/MEMPTFSI-modified electrode was much higher than that at the HRP/CP-modified electrode.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Enhanced Catalytic Activity of a de novo Enzyme in a Coacervate Phase

Biomolecular condensates are membraneless organelles that orchestrate various metabolic pathways in living cells. Understanding how these crowded structures regulate enzyme reactions remains yet challenging due to their dynamic and intricate nature. Coacervate microdroplets formed by associative liquid‐liquid phase separation of oppositely charged polyions have emerged as relevant condensate models to study enzyme catalysis. Enzyme reactions within these droplets show altered kinetics, influenced by factors such as enzyme and substrate partitioning, crowding, and interactions with coacervate components; it is often challenging to disentangle the contributions of each. Here, we investigate the peroxidase activity of a de novo enzyme within polysaccharide‐based coacervates. By comparing the reaction kinetics in buffer, in a suspension of coacervates and in the bulk coacervate phase collected after centrifugation of the droplets, we show that the coacervate phase significantly increases the enzyme catalytic efficiency. We demonstrate that the main origin of this enhanced activity lies in macromolecular crowding coupled to changes in the conformational dynamics of the enzyme within the coacervate environment. Altogether, these findings underline the crucial role of the coacervate matrix in enzyme catalysis, beyond simple partitioning effects. The observed boost in enzyme activity within the coacervate phase provides insights for designing biocatalytically active synthetic organelles.

Amplification- and Enzyme-Free Magnetic Diagnostics Circuit for Whole-Genome Detection of SARS-CoV-2 RNA.

Polymerase chain reaction (PCR) requires thermal cycling and enzymatic reactions for sequence amplification, hampering their applications in point-of-care (POC) settings. Magnetic bioassays based on magnetic particle spectroscopy (MPS) and magnetic nanoparticles (MNPs) are isothermal, wash-free, and can be quantitative. Realizing them amplification- and enzyme-free on a benchtop device, they will become irreplaceable for POC applications. Here we demonstrate a first-in-class magnetic signal amplification circuit (MAC) that enables detection of whole genome of SARS-CoV-2 by combining the specificity of toehold-mediated DNA strand displacement with the magnetic response of MNPs to declustering processes. Using MAC, we detect the N gene of SARS-CoV-2 samples at a concentration of 104 RNA copies/µl as determined by droplet digital PCR. Further, we demonstrate that MAC can reliably distinguish between SARS-CoV-2 and other human coronaviruses. Being a wash-, amplification- and enzyme-free biosensing concept and working at isothermal conditions (25 °C) on a low-cost benchtop MPS device, our MAC biosensing concept offers several indispensable features for translating nucleic acid detection to POC applications.

Cryoradiolysis of oxygenated cytochrome P450 17A1 with lyase substrates generates expected products

When subjected to γ-irradiation at cryogenic temperatures the oxygenated complexes of Cytochrome P450 CYP17A1 (CYP17A1) bound with either of the lyase substrates, 17α-Hydroxypregnenolone (17-OH PREG) or 17α-Hydroxyprogesterone (17-OH PROG) are shown to generate the corresponding lyase products, dehydroepiandrosterone (DHEA) and androstenedione (AD) respectively. The current study uses gas chromatography–mass spectrometry (GC/MS) to document the presence of the initial substrates and products in extracts of the processed samples. A rapid and efficient method for the simultaneous determination of residual substrate and products by GC/MS is described without derivatization of the products. It is also shown that no lyase products were detected for similarly treated control samples containing no nanodisc associated CYP17 enzyme, demonstrating that the product is formed during the enzymatic reaction and not by GC/MS conditions, nor the conditions produced by the cryoradiolysis process.

Novel foods, food enzymes, and food additives derived from food by-products of plant or animal origin: principles and overview of the EFSA safety assessment

The European Union (EU) is committed to transitioning toward a circular economy model, with food waste being one of the areas to be targeted. To close the loop of food waste generated during food processing and discarded at the retail or consumption phases, research and innovation parties proposed to valorize agro-food by-products to produce novel foods and food improvement agents (food additives, food enzymes, and food flavorings). In the EU, the authorization of such novel foods and food improvement agents is governed by different regulatory frameworks. A centralized safety assessment by the European Food Safety Authority (EFSA) is the prerequisite for their authorization through the so-called Union Lists. Up to December 2023, EFSA published 45 scientific opinions on the safety of novel foods, food enzymes, and food additives derived from by-products of plant and animal origin. The current study illustrates examples of these by-products for the production of novel foods or food improvement agents and the data requirements behind their respective safety assessments conducted by EFSA. In this review, applications on novel foods, food enzymes, and food additives received by EFSA were screened and analyzed to find the common scientific requirements and differences in terms of the safety evaluation of such products. Various by-products (i.e., corncobs, coffee husks, spent grains of barley and rice, grape pomace, pumpkin peels, bovine whey, eggshells, shrimp heads, and animal organs or tissues) were described in the applications as being processed (extraction, physical treatments, and chemical and enzymatic reactions) to obtain novel foods and food improvement agents. The heterogeneity and complexity of these products emphasize the challenge of their safety assessment, depending on the characteristics of each product. However, as this study shows, the scientific requirements underpinning their safety do not differ substantially in the different regulated product areas considered, with similar information needed to assess their safety in terms of identity, production process, compositional characterization, proposed/intended uses and exposure assessment, toxicological information, and allergenicity data. Additional nutritional information and data on the history of use are required in the case of novel foods.

3D Bioprinting of Sugar Beet Pectin through Horseradish Peroxidase-Catalyzed Cross-Linking.

Horseradish peroxidase (HRP)-mediated hydrogelation, caused by the cross-linking of phenolic groups in polymers in the presence of hydrogen peroxide (H2O2), is an effective route for bioink solidification in 3D bioprinting. Sugar beet pectin (SBP) naturally has cross-linkable phenols through the enzymatic reaction. Therefore, chemical modifications are not required, unlike the various polymers that have been used in the enzymatic cross-linking system. In this study, we report the application of SBP in extrusion-based bioprinting including HRP-mediated bioink solidification. In this system, H2O2 necessary for the solidification of inks is supplied in the gas phase. Cell-laden liver lobule-like constructs could be fabricated using bioinks consisting of 10 U/mL HRP, 4.0 and 6.0 w/v% SBP, and 6.0 × 106 cells/mL human hepatoblastoma (HepG2) cells exposed to air containing 16 ppm of H2O2 concurrently during printing and 10 min postprinting. The HepG2 cells enclosed in the printed constructs maintained their viability, metabolic activity, and hepatic functions from day 1 to day 7 of the culture, which indicates the cytocompatibility of this system. Taken together, this result demonstrates the potential of SBP and HRP cross-linking systems for 3D bioprinting, which can be applied in tissue engineering applications.

Positively Charged Biodegradable Polymersomes with Structure Inherent Fluorescence as Artificial Organelles.

Polymersomes, nanosized polymeric vesicles, have attracted significant interest in the areas of artificial cells and nanomedicine. Given their size, their visualization via confocal microscopy techniques is often achieved through the physical incorporation of fluorescent dyes, which however present challenges due to potential leaching. A promising alternative is the incorporation of molecules with aggregation-induced emission (AIE) behavior that are capable of fluorescing exclusively in their assembled state. Here, we report on the use of AIE polymersomes as artificial organelles, which are capable of undertaking enzymatic reactions in vitro. The ability of our polymersome-based artificial organelles to provide additional functionality to living cells was evaluated by encapsulating catalytic enzymes such as a combination of glucose oxidase/horseradish peroxidase (GOx/HRP) or β-galactosidase (β-gal). Via the additional incorporation of a pyridinium functionality, not only the cellular uptake is improved at low concentrations but also our platform's potential to specifically target mitochondria expands.

Enzymatic Reaction in a Capillary Microreactor with Surface-Immobilized Enzyme

Enzymatic Reaction in a Capillary Microreactor with Surface-Immobilized Enzyme

Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore.

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation-π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.

Assessment of the efficiency and stability of enzymatic membrane reaction utilizing lipase covalently immobilized on a functionalized hybrid membrane

Enzyme immobilization in membrane bioreactors has been considered as a practical approach to enhance the stability, reusability, and efficiency of enzymes. In this particular study, a new type of hybrid membrane reactor was created through the phase inversion method, utilizing hybrid of graphene oxide nanosheets (GON) and polyether sulfone (PES) in order to covalently immobilize the Candida rugosa lipase (CRL). The surface of hybrid membrane was initially modified by (3-Aminopropyl) triethoxysilane (APTES), before the use of glutaraldehyde (GLU), as a linker, through the imine bonds. The resulted enzymatic hybrid membrane reactors (EHMRs) were then thoroughly analyzed by using field-emission scanning electron microscopy (FE-SEM), contact angle goniometry, surface free energy analysis, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, attenuated total reflection (ATR), and energy-dispersive X-ray (EDX) spectroscopy. The study also looked into the impact of factors such as initial CRL concentration, storage conditions, and immobilization time on the EHMR's performance and activity, which were subsequently optimized. The results demonstrated that the CRLs covalently immobilized on the EHMRs displayed enhanced pH and thermal stability compared to those physically immobilized or free. These covalently immobilized CRLs could maintain over 60% of their activity even after 6 reaction cycles spanning 50 days. EHMRs are valuable biocatalysts in developing various industrial, environmental, and analytical processes.

A Systematic Review on Pesticide-loaded Nanocapsules: A Sustainable Route for Pesticide Management to Enhance Crop Productivity

Abstract: Synthetic pesticides, crucial compounds for agricultural production, degrade quickly and damage the environment, hence solutions for their decreased usage or formulations with prolonged efficacy at low dosages are needed. Nanotechnology for nanosized formulations may reduce pesticide adverse effects. Nano-encapsulated pesticides made from nanocapsules, nanoemulsions, micelles, and nanogels outperform traditional pesticides with minimum environmental impact. Nanopesticides allowed target-based administration to decrease leaching and drainage into water bodies, and lower pesticide active component dosages. Nanocapsules with a core-shell configuration and a pesticide in the core are the most advantageous nanomaterials. Nanocapsules shield the active component. Stimuli-responsive nanocapsules may limit pesticide release by responding to pH, temperature, light, enzyme, or redox reactions. Toxicity prevents their use. This review discusses the latest developments in nanocapsule fabrication methods, their relevance, contemporary synthetic approaches to developing pesticide-loaded nanocapsules, and the features of these nanocomposites, with an emphasis on sustainable agricultural applications.

Synthesis, kinetic studies, and QSAR of dinucleoside polyphosphate derivatives as human AK1 inhibitors

Adenylate kinase (AK) plays a crucial role in the metabolic monitoring of cellular adenine nucleotide homeostasis by catalyzing the reversible transfer of a phosphate group between ATP and AMP, yielding two ADP molecules. By regulating the nucleotide levels and energy metabolism, the enzyme is considered a disease modifier and potential therapeutic target for various human diseases, including malignancies and inflammatory and neurodegenerative disorders. However, lacking approved drugs targeting AK hinders broad studies on this enzyme's pathological importance and therapeutic potentialIn this work, we determined the effect of a series of dinucleoside polyphosphate derivatives, commercially available (11 compounds) and newly synthesized (8 compounds), on the catalytic activity of human adenylate kinase isoenzyme 1 (hAK1). The tested compounds belonged to the following groups: (1) diadenosine polyphosphates with different phosphate chain lengths, (2) base-modified derivatives, and (3) phosphate-modified derivatives. We found that all the investigated compounds inhibited the catalytic activity of hAK1, yet with different efficiencies. Three dinucleoside polyphosphates showed IC50 values below 1 µM, and the most significant inhibitory effect was observed for P1-(5′-adenosyl) P5-(5′-adenosyl) pentaphosphate (Ap5A). To understand the observed differences in the inhibition efficiency of the tested dinucleoside polyphosphates, the molecular docking of these compounds to hAK1 was performed. Finally, we conducted a quantitative structure–activity relationship (QSAR) analysis to establish a computational prediction model for hAK1 modulators. Two PLS-regression-based models were built using kinetic data obtained from the AK1 activity analysis performed in both directions of the enzymatic reaction. Model 1 (AMP and ATP synthesis) had a good prediction power (R2 = 0.931, Q2 = 0.854, and MAE = 0.286), while Model 2 (ADP synthesis) exhibited a moderate quality (R2 = 0.913, Q2 = 0.848, and MAE = 0.370). These studies can help better understand the interactions between dinucleoside polyphosphates and adenylate kinase to attain more effective and selective inhibitors in the future.

A weighted combination of reproducing kernel particle shape functions with cardinal functions of scalable polyharmonic spline radial kernel utilized in Galerkin weak form of a mathematical model related to anti-angiogenic therapy

In this manuscript, a new localized meshfree (meshless) approximation, i.e., a combination of the reproducing kernel particle (RKP) shape functions with the cardinal functions based on the scalable polyharmonic spline (PHS) radial function is introduced. It is called the RKP+PHS+poly approximation, and its convergence rate is of order O(hm+1), where m is the total degree of polynomials. We apply this method to construct the spaces of trial and test functions in a Galerkin scheme of an extended version of the biological mathematical model in two dimensions describing the interactions between endothelial cells, fibronectin, angiogenic growth factors, and fasentin concentrations. By considering the row-sum method, the eigenvalue stability is also numerically carried out for the discrete equations corresponding to the obtained weak formulation. Accordingly, a semi-implicit form of the backward difference method of order 1 (SBDF1) has been utilized to approximate the weak form in time. We complete our numerical algorithm by solving the obtained full-discretized problem overtime via the biconjugate gradient stabilized (BiCGSTAB) solver with a proper preconditioner. Some simulation results are investigated by estimating the maximum velocity parameter of an enzymatic reaction from the experimental dose–response curve of fasentin to demonstrate the effect of using fasentin drug.