From Molecular Dynamics to Taste Sensory Perception: A Comprehensive Study on the Interaction of Umami Peptides with the T1R1/T1R3-VFT Receptor.

The research on the umami receptor-ligand interaction is crucial for understanding umami perception. This study integrated molecular simulations, sensory evaluation, and biosensor technology to analyze the interaction between umami peptides and the umami receptor T1R1/T1R3-VFT. Molecular dynamics simulations were used to investigate the dissociation process of seven umami peptides with the umami receptor T1R1/T1R3-VFT, and by calculating the potential mean force curve using the Jarzynski equation, it was found that the binding free energy of umami peptide is between -58.80 and -12.17 kcal/mol, which had a strong correlation with the umami intensity obtained by time intensity sensory evaluation. Through correlation analysis, the dissociation rate constants (0.0126-0.394 1/s) of umami peptides were found to have a great impact on umami perception. The faster the dissociation rate of umami peptides from receptors, the stronger the perceived intensity of the umami taste. This research aims to elucidate the relationship between the umami peptide-receptor interaction and umami perception, providing theoretical support for the exploration of umami perception mechanisms.

Noteworthy Consensus Effects of D/E Residues in Umami Peptides Used for Designing the Novel Umami Peptides.

Aspartic acid (D) and glutamic acid (E) play vital roles in the umami peptides. To understand their exact mechanism of action, umami peptides were collected and cut into 1/2/3/4 fragments. Connecting D/E to the N/C-termini of the fragments formed D/E consensus effect groups (DEEGs), and all fragments containing DEEG were summarized according to the ratio and ranking obtained in the above four situations. The interaction patterns between peptides in DEEG and T1R1/T1R3-VFD were compared by statistical analysis and molecular docking, and the most conservative contacts were found to be HdB_277_ARG and HdB_148_SER. The molecular docking score of the effector peptides significantly dropped compared to that of their original peptides (-1.076 ± 0.658 kcal/mol, p value < 0.05). Six types of consensus fingerprints were set according to the Top7 contacts. The exponential of relative umami was linearly correlated with ΔGbind (R2 = 0.961). Under the D/E consensus effect, the electrostatic effect of the umami peptide was improved, and the energy gap between the highest occupied molecular orbital-the least unoccupied molecular orbital (HOMO-LUMO) was decreased. The shortest path map showed that the peptides had similar T1R1-T1R3 recognition pathways. This study helps to reveal umami perception rules and provides support for the efficient screening of umami peptides based on the material richness in D/E sequences.

Bimetallic bionic taste sensor for perception of the synergistic effect of umami substances.

Synergistic effect is one of the main properties of umami substances, elucidating the synergistic effect of umami is of great significance in the food industry. In this study, a bimetallic bionic taste sensor was developed to evaluate the synergistic effect of umami substances based on the perceptual mechanism of the human taste system. The Venus flytrap domain of T1R1 which is in charge of recognizing umami ligands was employed as the sensing element and self-assembled on the bimetallic nanomaterial (MoS2-PtPd) by Au-S bonding, the binding of receptors and ligands is characterized by changes of electrical signals. The sensor had good linearity (R2 > 0.99) and wide detection range in the detection of different kinds of umami substances (amino acids, nucleotides, organic acids, umami peptides) with detection limits as low as 0.03 pM. Comparing with electronic tongues, the sensor owned multiple characteristics of human taste system and could recognize the presence of synergistic effect of umami substances in a variety of real samples. Moreover, the differences in synergistic effect at different concentrations and ratios were also explored, the findings showed that the synergistic effect was more obvious at lower concentrations and balanced ratios of multiple umami substances added. The strategy would afford a promising platform for in-depth research on the mechanism of synergistic effect and multifunctional industrial applications.

Conserved Sites and Recognition Mechanisms of T1R1 and T2R14 Receptors Revealed by Ensemble Docking and Molecular Descriptors and Fingerprints Combined with Machine Learning.

Taste peptides, as an important component of protein-rich foodstuffs, potentiate the nutrition and taste of food. Thereinto, umami- and bitter-taste peptides have been ex tensively reported, while their taste mechanisms remain unclear. Meanwhile, the identification of taste peptides is still a time-consuming and costly task. In this study, 489 peptides with umami/bitter taste from TPDB (http://tastepeptides-meta.com/) were collected and used to train the classification models based on docking analysis, molecular descriptors (MDs), and molecular fingerprints (FPs). A consensus model, taste peptide docking machine (TPDM), was generated based on five learning algorithms (linear regression, random forest, gaussian naive bayes, gradient boosting tree, and stochastic gradient descent) and four molecular representation schemes. Model interpretive analysis showed that MDs (VSA_EState, MinEstateIndex, MolLogP) and FPs (598, 322, 952) had the greatest impact on the umami/bitter prediction of peptides. Based on the consensus docking results, we obtained the key recognition modes of umami/bitter receptors (T1Rs/T2Rs): (1) residues 107S-109S, 148S-154T, 247F-249A mainly form hydrogen bonding contacts and (2) residues 153A-158L, 163L, 181Q, 218D, 247F-249A in T1R1 and 56D, 106P, 107V, 152V-156F, 173K-180F in T2R14 constituted their hydrogen bond pockets. The model is available at http://www.tastepeptides-meta.com/yyds.

Ultrasensitive electrochemiluminescence aptasensor based on ABEI reduced silver nanoparticles for the detection of profenofos.

An ultrasensitive electrochemiluminescence (ECL) aptasensor for detection of profenofos was constructed by the reducibility and chemiluminescence property of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). ABEI was used to reduce silver nitrate (AgNO3) to silver nanoparticles (AgNPs), which could be adsorbed on the lattice of graphene oxide (GO) to form ABEI-AgNPs-GO complex. This compound could achieve excellent luminescence. The aptamer (Apt) modified (5') by sulfhydryl groups could be immobilized on AgNPs to capture profenofos. When profenofos was present, the ECL signal of the aptasensor would be weakened. To further demonstrate the successful construction of the aptasensor, cyclic voltammetry tests were performed on an electrochemical workstation and an ECL analyzer, respectively. The standard curve and specificity experiment both showed that the sensor had the advantages of low limit of detection (LOD) and good specificity. Under the optimal conditions, the aptasensor had a good linear response for profenofos in the range of 1 × 10-1-1 × 104 ng/mL. It also had a LOD of 6.7 × 10-2 ng/mL and a correlation coefficient (R2) of 0.9991. The aptasensor had been successfully applied to the detection of profenofos in vegetables. The recovery range of the proposed ECL aptasensor was 98 % ~ 107.4 %.

Dual-Target Electrochemical Sensor Based on 3D MoS2-rGO and Aptamer Functionalized Probes for Simultaneous Detection of Mycotoxins.

A dual-target aptamer functionalized probes (DTAFP) was applied for the detection of aflatoxin B1 (AFB1) and zearalenone (ZEN) simultaneously, which has not been reported. Meanwhile, two functional materials for signal amplification of the DTAFP were synthesized: 1) a three-dimensional molybdenum disulfide-reduced graphene oxide (MoS2-rGO) as a favorable loading interface; 2) a double-probes gold nanoparticles (AuNPs) modified by Thionin (Thi) and 6-(Ferrocenyl) hexanethiol (FC6S) as distinguishable and non-interfering signals. Mycotoxins on the electrode surface release into solution under the function of the DTAFP, leading a reduction of the differential peak impulse in signal response. Under the optimum conditions, the aptasensor exhibited a detection range of 1.0 pg mL-1-100 ng mL-1 for AFB1 and ZEN, with no observable cross reactivity. In addition, the aptasensor performed excellent stability, reproducibility, specificity, and favorable recovery in the detection of edible oil. This work demonstrated a novel method for the construction of a simple, rapid, and sensitive aptasensor in the detection of multiple mycotoxins simultaneously.

Mechanical behavior and constitutive model for loess samples under simulated acid rain conditions.

Acid rain is mainly composed of sulfuric acid and nitric acid aqueous solutions, which can deteriorate the mechanical properties of soil and thus threaten the safety of soil engineerings. In this paper, the influence of sulfuric acid rain on mechanical properties of loess soil samples was studied. The diluted sulfuric acid solution has respectively pH 5.0, 4.0 and 3.0 to simulate the acid rain condition, and the triaxial compressional tests and scanning electron microscope were carried out to investigate the deteriorated properties and evolution of the microstructure of the saturated loess samples. The results demonstrated that acid rain made the porosity of loess samples larger, and changed the pore distribution and contacts of soil grains, so that the mechanical properties of loess samples varied in some degree. With the decrease of pH value, both the peak value of the deviatoric stress and volumetric contraction of loess samples decreased, which reduced the parameters of shear strength of loess samples. Furthermore, a framework of the chemical-mechanical model for loess under the action of acid rain was established, in which loess was considered as a porous medium material, and the influences of acid rain with different pH values were taken into account in the double-hardening constitutive model, and the model was also verified by the triaxial test results finally.

In vitro evidence for endocrine-disrupting chemical (EDC)'s inhibition of drug metabolism.

BACKGROUND: Humans can be frequently exposed to Bisphenol A (BPA) via multiple sources, and babies are considered to be the most sensitive group to exposure of BPA. AIMS: To investigate the inhibition potential of BPA towards human liver microsomes (HLMs)-catalyzed zidovudine (AZT) glucuronidation. MATERIALS AND METHODS: In vitro HLMs incubation system was used to investigate the inhibition potential of BPA towards AZT glucuronidation. Both Dixon and Lineweaver-Burk plots were employed to determine the inhibition kinetic type, and nonlinear repression was utilized to calculate the inhibition kinetic parameters (Ki). RESULTS: Concentration-dependent inhibition of BPA towards AZT glucuronidation was observed. Both Dixon and Lineweaver-Burk plots showed that BPA exerted competitive inhibition towards the glucuronidation of AZT, and nonlinear repression with competitive equation was used to calculate the Ki value to be 3.2 µM. CONCLUSION: Potential BPA-AZT interaction might occur when the patients administered with AZT is also exposed to BPA.