Neoculin is a sweet protein capable to alter the sour taste into sweet taste, it is 500 times sweeter than the ordinary sugar. This protein has been discovered in Malaysia under the name of Curculin. There are a number of experimental studies that have been conducted on neoculin but none of the studies focuses on molecular level, in order to understand how the protein interacts with the human sweet taste receptors T1R2 and T1R3. Therefore, in this work, a protein-protein docking study was performed between neoculin and the human sweet taste receptor T1R2 and T1R3. The docking results showed residues that might be important for binding the neoculin with the human sweet taste receptors, particularly T1R3 at the amino terminal domain (ATD). In addition, the current results showed that His11, which is important for the taste modifying ability does not bind directly to the human sweet taste receptors.
The application of protein-protein interaction (PPI) has been widely used in various industries, such as food, nutraceutical, and pharmaceutical. A deeper understanding of PPI is needed, and the molecular forces governing proteins and their interaction must be explained. The design of new structures with improved functional properties, e.g., solubility, emulsion, and gelation, has been fueled by the development of structural and colloidal building blocks. In this review, the molecular forces of protein structures are discussed, followed by the relationship between molecular force and structure, ways of a bind of proteins together in solution or at the interface, and functional properties. A more detailed look is thus taken at the relationship between the various influencing factors on molecular forces involved in PPI. These factors include protein properties, such as types, concentration, and mixing ratio, and solvent conditions, such as ionic strength and pH. This review also summarizes methods tha1t are capable of identifying molecular forces in protein and PPI, as well as characterizing protein structure.
This article presents the assessment of time-dependent national-level restrictions and control actions and their effects in fighting the COVID-19 pandemic. By analysing the transmission dynamics during the first wave of COVID-19 in the country, the effectiveness of the various levels of control actions taken to flatten the curve can be better quantified and understood. This in turn can help the relevant authorities to better plan for and control the subsequent waves of the pandemic. To achieve this, a deterministic population model for the pandemic is firstly developed to take into consideration the time-dependent characteristics of the model parameters, especially on the ever-evolving value of the reproduction number, which is one of the critical measures used to describe the transmission dynamics of this pandemic. The reproduction number alongside other key parameters of the model can then be estimated by fitting the model to real-world data using numerical optimisation techniques or by inducing ad-hoc control actions as recorded in the news platforms. In this article, the model is verified using a case study based on the data from the first wave of COVID-19 in the Republic of Kazakhstan. The model is fitted to provide estimates for two settings in simulations; time-invariant and time-varying (with bounded constraints) parameters. Finally, some forecasts are made using four scenarios with time-dependent control measures so as to determine which would reflect on the actual situations better.
In this work, a chitosan-modified nanofiber membrane was fabricated and used to examine the permeation characteristics of C-phycocyanin (CPC) obtained from Spirulina platensis. The effects of NaCl concentration (0.1-1.0 M), chitosan coupling pH (6-8), chitosan coupling concentration (0.1-3.0%), algal solution pH (6-8), algal mass concentration (0.1-1.0% dw/v), and membrane flux (4.08 × 10-2-2.04 × 10-1 mL/min·cm2) on the penetration performance of the membrane for CPC were investigated. The results show that the order of binding selectivity of the membrane for these proteins is contaminating proteins (TP) > allophycocyanin (APC) > CPC. TP and APC molecules were more easily adsorbed by the chitosan-modified membrane, and the CPC molecules most easily penetrated the membrane without being adsorbed, enhancing CPC purity. The purification factor and total mass flux were 3.3 fold and 66%, respectively, in a single step.
Tyrphostin 9 (Tyr 9) is a potent platelet-derived growth factor receptor (PDGFR) inhibitor, which induces apoptosis in various cancer cell types. The binding of Tyr 9 to the major transport protein, human serum albumin (HSA) was investigated using several spectroscopic techniques and molecular docking method. Fluorescence quenching titration results showed progressive decrease in the protein fluorescence with increasing drug concentrations. A decreasing trend of the Stern-Volmer constant, Ksv with increasing temperature characterized the drug-induced quenching as static quenching, thus pointed towards the formation of Tyr 9-HSA complex. The binding constant of Tyr 9-HSA interaction was found to lie within the range 3.48-1.69 × 105 M-1 at three different temperatures, i.e. 15 °C, 25 °C and 35 °C, respectively and suggested intermediate binding affinity between Tyr 9 and HSA. The drug-HSA complex seems to be stabilized by hydrophobic forces, van der Waals forces and hydrogen bonds, as suggested from the thermodynamic data as well as molecular docking results. The far-UV and the near-UV CD spectral results showed slight alteration in the secondary and tertiary structures, respectively, of the protein upon Tyr 9 binding. Interaction of Tyr 9 with HSA also produced microenvironmental perturbations around protein fluorophores, as evident from the three-dimensional fluorescence spectral results but increased protein's thermal stability. Both competitive drug binding results and molecular docking analysis suggested Sudlow's Site I of HSA as the preferred Tyr 9 binding site. Communicated by Ramaswamy H. Sarma.
Clinacanthus nutans has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of C. nutans compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of C. nutans satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of C. nutans compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.
In order to invent a porcine gelatine detection device using microbial resources, bacterial enzymes with a preference towards porcine gelatine and their candidate genes were evaluated. Five (n = 5) bacterial strains isolated from hot spring water and wet clay, Malaysia were screened for their gelatinase activity. The gelatinase enzyme was extracted and purified using ammonium sulphate precipitation prior to performing gelatinase assay on porcine, bovine and fish gelatine medium substrates. The G2 strain or Enterobacter aerogenes (Strain EA1) was selected for whole genome sequenced after showing a consistent trend of preference towards porcine gelatine. The gelatinase candidate gene gelEA1_9 was cloned and expressed. Based on one-way analysis of variance (ANOVA) with POST-HOC Duncan test (α = 0.05), the final product of gelEA1_9 was identified as a novel gelatinase. This gelatinase presented no significant difference in activity towards porcine gelatine. Hence, the present study demonstrated an enzyme-substrate interaction for porcine gelatine identification.
The high dependency and surplus use of agrochemical products have liberated enormous quantities of toxic halogenated pollutants into the environment and threaten the well-being of humankind. Herein, this study performed molecular docking, molecular dynamic (MD) simulations, molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations on the DehH2 from Bacillus thuringiensis, to identify the order of which the enzyme degrades different substrates, haloacids, haloacetate and chlorpyrifos. The study discovered that the DehH2 favored the degradation of haloacids and haloacetates (-3.3 - 4.6 kcal/mol) and formed three hydrogen bonds with Asp125, Arg201 and Lys202. Despite the inconclusive molecular docking result, chlorpyrifos was consistently shown to be the least favored substrate of the DehH2 in MD simulations and MM-PBSA calculations. Results of MD simulations revealed the DehH2-haloacid- (RMSD 0.15 - 0.25 nm) and DehH2-haloacetates (RMSF 0.05 - 0.25 nm) were more stable, with the DehH2-L-2CP complex being the most stable while the least was the DehH2-chlorpyrifos (RMSD 0.295 nm; RMSF 0.05 - 0.59 nm). The Molecular Mechanics Poisson-Boltzmann Surface Area calculations showed the DehH2-L-2CP complex (-24.27 kcal/mol) having the lowest binding energy followed by DehH2-MCA (-22.78 kcal/mol), DehH2-D-2CP (-21.82 kcal/mol), DehH2-3CP (-21.11 kcal/mol), DehH2-2,2-DCP (-18.34 kcal/mol), DehH2-2,3-DCP (-8.34 kcal/mol), DehH2-TCA (-7.62 kcal/mol), while chlorpyrifos was unable to spontaneously bind to DehH2 (+127.16 kcal/mol). In a nutshell, the findings of this study offer valuable insights into the rational tailoring of the DehH2 for expanding its substrate specificity and catalytic activity in the near future.Communicated by Ramaswamy H. Sarma.
In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.
Surface functionalization of multi-walled carbon nanotubes (MWCNTs) was carried out using a gas phase treatment in a Universal Temperature Program (UTP) reactor by flowing SO3 gas onto the CNTs while being heated at different temperatures. The functionalized nanotubes were characterized using X-ray Fluorescence (XRF), Fourier Transform Infrared Spectroscopy (FT-IR) and Raman spectroscopy. The amount of oxyen and sulfur containing groups was determined by acid-base titration. The titration results were in good agreement with elemental analysis using x-ray fluorescence. FTIRanalysis showed the presence of oxygen and sulfur containing groups, S=O, C-S, C=O and -COOH. Raman spectroscopy confirmed that oxygen and sulfur containing acidic groups covalently attached to the sidewall of the MWCNTs.
Interaction of an anticancer drug, vandetanib (VDB) with a ligand transporter, lysozyme (LYZ) was explored using multispectroscopic techniques, such as fluorescence, absorption and circular dichroism along with computational analysis. Fluorescence data and absorption results confirmed VDB-LYZ complexation. VDB-induced quenching was characterized as static quenching based on inverse correlation of KSV with temperature as well as kq values. The complex was characterized by the weak binding constant (Ka=4.96-3.14×103M-1). Thermodynamic data (ΔS=+12.82Jmol-1K-1; ΔH=-16.73kJmol-1) of VDB-LYZ interaction revealed participation of hydrophobic and van der Waals forces along with hydrogen bonds in VDB-LYZ complexation. Microenvironmental perturbations around tryptophan and tyrosine residues as well as secondary and tertiary structural alterations in LYZ upon addition of VDB were evident from the 3-D fluorescence, far- and near-UV CD spectral analyses, respectively. Interestingly, addition of VDB to LYZ significantly increased protein's thermostability. Molecular docking results suggested the location of VDB binding site near the LYZ active site while molecular dynamics simulation results suggested stability of VDB-LYZ complex. Presence of Mg2+, Ba2+ and Zn2+ was found to interfere with VDB-LYZ interaction.
A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot three-component classical Kabachnik-Fields reaction in a green chemical approach by addition of an in situ generated dialkylphosphite to Schiff's base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2-alkylaminophosphonates were screened to in vitro antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. These in vitro studies have been further supported by ADMET (absorption, distribution, metabolism, excretion, and toxicity), quantitative structure-activity relationship, molecular docking, and bioactivity studies and identified that they were potentially bound to the GLN340 amino acid residue in chain C of 1DNU protein and TYR597 amino acid residue in chain A of 4M7E protein, causing potential exhibition of antioxidant and plant growth regulatory activities. Eventually, title compounds are identified as good blood-brain barrier (BBB)-penetrable compounds and are considered as proficient central nervous system active and neuroprotective antioxidant agents as the neuroprotective property is determined with BBB penetration thresholds.
The present study reported a facile method for the determination of melamine in milk powder products based on the aggregation of reactant-free 5 nm gold nanoparticles (AuNPs). The strong electrostatic attraction between the positively charged exocyclic amine groups present in the melamine molecule and the negatively charged ions bound to the AuNPs induced aggregation of the AuNPs, resulting in visible color changes that could be seen with the naked eye and monitored by ultraviolet-visible (UV-Vis) absorbance spectra. The method shows high sensitivity with detection limits of 1 × 10-9 M for visual detection and 1 × 10-11 M for UV-Vis analysis, which is far below the safety limit of melamine ingestion in infant formula (1 ppm = 7.9 × 10-6 M) and the detection limit acquired by most AuNP-based melamine detection methods. Good recoveries were obtained over the range of 94.7-95.5% with a relative standard deviation of mean recovery (RSD) ranging from 1.40 to 5.81. The method provides a simple, feasible, fast and real-time detection of melamine adulterants in infant formula by the naked eye, without the aid of advanced instruments.