RESUMEN
The sense of smell is a biological process involving volatile molecules that interact with proteins called olfactory receptors to transmit a nervous message that allows the recognition of a perceived odor. However, the relationships between odorant molecules, olfactory receptors and odors (O3) are far from being well understood due to the combinatorial olfactory codes and large family of olfactory receptors. This is the reason why, based on 5802 odorant molecules and their annotations to 863 olfactory receptors (human) and 7029 odors and flavors annotations, a web server called Pred-O3 has been designed to provide insights into olfaction. Predictive models based on Artificial Intelligence have been developed allowing to suggest olfactory receptors and odors associated with a new molecule. In addition, based on the encoding of the odorant molecule's structure, physicochemical features related to odors and/or olfactory receptors are proposed. Finally, based on the structural models of the 98 olfactory receptors a systematic docking protocol can be applied and suggest if a molecule can bind or not to an olfactory receptor. Therefore, Pred-O3 is well suited to aid in the design of new odorant molecules and assist in fragrance research and sensory neuroscience. Pred-O3 is accessible at ' https://odor.rpbs.univ-paris-diderot.fr/'.
Asunto(s)
Internet , Odorantes , Receptores Odorantes , Programas Informáticos , Receptores Odorantes/metabolismo , Receptores Odorantes/química , Receptores Odorantes/genética , Humanos , Simulación del Acoplamiento Molecular , Olfato/fisiologíaRESUMEN
Flavor is perceived through the olfactory, taste, and trigeminal systems, mediated by designated GPCRs and channels. Signal integration occurs mainly in the brain, but some cross-reactivities occur at the receptor level. Here, we predict potential bitterness and taste receptors targets for thousands of odorants. BitterPredict and BitterIntense classifiers suggest that 3-9% of flavor and food odorants have bitter taste, but almost none are intensely bitter. About 14% of bitter molecules are expected to have an odor. Bitterness is more common for unpleasant smells such as fishy, amine, and ammoniacal, while non-bitter odorants often have pleasant smells. Experimental toxicity values suggest that fishy ammoniac smells are more toxic than pleasant smells, regardless of bitterness. TAS2R14 is predicted as the main bitter receptor for odorants, confirmed by in vitro profiling of 10 odorants. The activity of bitter odorants may have implications for physiology due to ectopic expression of taste and smell receptors.
Asunto(s)
Neuronas Receptoras Olfatorias , Gusto , Humanos , Gusto/fisiología , Odorantes/análisis , Percepción del Gusto/fisiología , Olfato , Neuronas Receptoras Olfatorias/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
The mechanisms involved in the homogeneous perception of odorant mixtures remain largely unknown. With the aim of enhancing knowledge about blending and masking mixture perceptions, we focused on structure-odor relationships by combining the classification and pharmacophore approaches. We built a dataset of about 5000 molecules and their related odors and reduced the multidimensional space defined by 1014 fingerprints representing the structures to a tridimensional 3D space using uniform manifold approximation and projection (UMAP). The self-organizing map (SOM) classification was then performed using the 3D coordinates in the UMAP space that defined specific clusters. We explored the allocating in these clusters of the components of two aroma mixtures: a blended mixture (red cordial (RC) mixture, 6 molecules) and a masking binary mixture (isoamyl acetate/whiskey-lactone [IA/WL]). Focusing on clusters containing the components of the mixtures, we looked at the odor notes carried by the molecules belonging to these clusters and also at their structural features by pharmacophore modeling (PHASE). The obtained pharmacophore models suggest that WL and IA could have a common binding site(s) at the peripheral level, but that would be excluded for the components of RC. In vitro experiments will soon be carried out to assess these hypotheses.
Asunto(s)
Percepción Olfatoria , Odorantes , Farmacóforo , Algoritmos , OlfatoRESUMEN
Deciphering the relationship between molecules, olfactory receptors (ORs) and corresponding odors remains a challenging task. It requires a comprehensive identification of ORs responding to a given odorant. With the recent advances in artificial intelligence and the growing research in decoding the human olfactory perception from chemical features of odorant molecules, the applications of advanced machine learning have been revived. In this study, Convolutional Neural Network (CNN) and Graphical Convolutional Network (GCN) models have been developed on odorant molecules-odors and odorant molecules-olfactory receptors using a large set of 5955 molecules, 160 odors and 106 olfactory receptors. The performance of such models is promising with a Precision/Recall Area Under Curve of 0.66 for the odorant-odor and 0.91 for the odorant-olfactory receptor GCN models respectively. Furthermore, based on the correspondence of odors and ORs associated for a set of 389 compounds, an odor-olfactory receptor pairwise score was computed for each odor-OR combination allowing to suggest a combinatorial relationship between olfactory receptors and odors. Overall, this analysis demonstrate that artificial intelligence may pave the way in the identification of the smell perception and the full repertoire of receptors for a given odorant molecule.
Asunto(s)
Percepción Olfatoria , Neuronas Receptoras Olfatorias , Receptores Odorantes , Humanos , Inteligencia Artificial , Odorantes , OlfatoRESUMEN
This study aims to highlight the relationships between the structure of smell compounds and their odors. For this purpose, heterogeneous data sources were screened, and 6038 odorant compounds and their known associated odors (162 odor notes) were compiled, each individual molecule being represented with a set of 1024 structural fingerprint. Several dimensional reduction techniques (PCA, MDS, t-SNE and UMAP) with two clustering methods (k-means and agglomerative hierarchical clustering AHC) were assessed based on the calculated fingerprints. The combination of UMAP with k-means and AHC methods allowed to obtain a good representativeness of odors by clusters, as well as the best visualization of the proximity of odorants on the basis of their molecular structures. The presence or absence of molecular substructures has been calculated on odorant in order to link chemical groups to odors. The results of this analysis bring out some associations for both the odor notes and the chemical structures of the molecules such as "woody" and "spicy" notes with allylic and bicyclic structures, "balsamic" notes with unsaturated rings, both "sulfurous" and "citrus" with aldehydes, alcohols, carboxylic acids, amines and sulfur compounds, and "oily", "fatty" and "fruity" characterized by esters and with long carbon chains. Overall, the use of UMAP associated to clustering is a promising method to suggest hypotheses on the odorant structure-odor relationships.
Asunto(s)
Odorantes/análisis , Olfato , Análisis por Conglomerados , Conformación Molecular , Análisis de Escalamiento Multidimensional , Análisis de Componente PrincipalRESUMEN
The perception of aroma mixtures is based on interactions beginning at the peripheral olfactory system, but the process remains poorly understood. The perception of a mixture of ethyl isobutyrate (Et-iB, strawberry-like odor) and ethyl maltol (Et-M, caramel-like odor) was investigated previously in both human and animal studies. In those studies, the binary mixture of Et-iB and Et-M was found to be configurally processed. In humans, the mixture was judged as more typical of a pineapple odor, similar to allyl hexanoate (Al-H, pineapple-like odor), than the odors of the individual components. To explore the key features of this aroma blend, we developed an in silico approach based on molecules having at least one of the odors-strawberry, caramel or pineapple. A dataset of 293 molecules and their related odors was built. We applied the notion of a "social network" to describe the network of the odors. Additionally, we explored the structural properties of the molecules in this dataset. The network of the odors revealed peculiar links between odors, while the structural study emphasized key characteristics of the molecules. The association between "strawberry" and "caramel" notes, as well as the structural diversity of the "strawberry" molecules, were notable. Such elements would be key to identifying potential odors/odorants to form aroma blends.
Asunto(s)
Odorantes , Ananas , Interpretación Estadística de Datos , Bases de Datos de Compuestos Químicos , Fragaria , Humanos , Isomerismo , Modelos Teóricos , Estructura Molecular , Peso Molecular , Percepción Olfatoria , Propionatos , PironasRESUMEN
Odor-taste association has been successfully applied to enhance taste perception in foods with low sugar or low salt content. Nevertheless, selecting odor descriptors with a given associated taste remains a challenge. In the aim to look for odors able to enhance some specific taste, we tested different multivariate analyses to find links between taste descriptors and odor descriptors, starting from a set of data previously obtained using gas chromatography/olfactometry-associated taste: 68 odorant zones described with 41 odor descriptors and 4 taste-associated descriptors (sweetness, saltiness, bitterness, and sourness). A partial least square analysis allowed for identification of odors associated with a specific taste. For instance, odors described as either fruity, sweet, strawberry, candy, floral, or orange are associated with sweetness, while odors described as either toasted, potato, sulfur, or mushroom are associated with saltiness. A network representation allowed for visualization of the links between odor and taste descriptors. As an example, a positive association was found between butter odor and both saltiness and sweetness. Our approach provided a visualization tool of the links between odor and taste description and could be used to select odor-active molecules with a potential taste enhancement effect based on their odor descriptors.
Asunto(s)
Aromatizantes/análisis , Odorantes/análisis , Humanos , Análisis Multivariante , Olfato , GustoRESUMEN
Habituation is a filter that optimizes the processing of information by our brain in all sensory modalities. It results in an unconscious reduced responsiveness to continuous or repetitive stimulation. In olfaction, the main question is whether habituation works the same way for any odorant or whether we habituate differently to each odorant? In particular, whether chemical, physical or perceptual cues can limit or increase habituation. To test this, the odour intensity of 32 odorants differing in physicochemical characteristics was rated by 58 participants continuously during 120s. Each odorant was delivered at a constant concentration. Results showed odorants differed significantly in habituation, highlighting the multifactoriality of habituation. Additionally habituation was predicted from 15 physico-chemical and perceptual characteristics of the odorants. The analysis highlighted the importance of trigeminality which is highly correlated to intensity and pleasantness. The vapour pressure, the molecular weight, the Odor Activity Value (OAV) and the number of double bonds mostly contributed to the modulation of habituation. Moreover, length of the carbon chain, number of conformers and hydrophobicity contributed to a lesser extent to the modulation of habituation. These results highlight new principles involved in the fundamental process of habituation, notably trigeminality and the physicochemical characteristics associated.
Asunto(s)
Habituación Psicofisiológica , Olfato , Adulto , Fenómenos Químicos , Femenino , Humanos , Masculino , Odorantes , Adulto JovenRESUMEN
This chapter describes the main characteristics of olfactory receptor (OR) genes of vertebrates, including generation of this large multigenic family and pseudogenization. OR genes are compared in relation to evolution and among species. OR gene structure and selection of a given gene for expression in an olfactory sensory neuron (OSN) are tackled. The specificities of OR proteins, their expression, and their function are presented. The expression of OR proteins in locations other than the nasal cavity is regulated by different mechanisms, and ORs display various additional functions. A conventional olfactory signal transduction cascade is observed in OSNs, but individual ORs can also mediate different signaling pathways, through the involvement of other molecular partners and depending on the odorant ligand encountered. ORs are engaged in constitutive dimers. Ligand binding induces conformational changes in the ORs that regulate their level of activity depending on odorant dose. When present, odorant binding proteins induce an allosteric modulation of OR activity. Since no 3D structure of an OR has been yet resolved, modeling has to be performed using the closest G-protein-coupled receptor 3D structures available, to facilitate virtual ligand screening using the models. The study of odorant binding modes and affinities may infer best-bet OR ligands, to be subsequently checked experimentally. The relationship between spatial and steric features of odorants and their activity in terms of perceived odor quality are also fields of research that development of computing tools may enhance.
Asunto(s)
Imagenología Tridimensional , Odorantes/análisis , Mucosa Olfatoria/fisiología , Receptores Odorantes/química , Receptores Odorantes/fisiología , Animales , Humanos , Relación Estructura-ActividadRESUMEN
The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome.
Asunto(s)
Mapeo Cromosómico/métodos , Genoma Humano/fisiología , Receptores Odorantes/genética , Humanos , PPAR gamma/genética , PPAR gamma/metabolismo , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Receptores Odorantes/metabolismoRESUMEN
The phase ratio variation PRV method is a classical way to determine the partition coefficients of volatile compounds between their solution and vapour phases in a variety of circumstances. However, some results obtained by this method can be disappointing. A new PRV equation in which the initial liquid-phase solute concentration is replaced by the liquid-phase solute concentration at equilibrium is proposed. This proposed PRV equation is a second-order polynomial equation. To thoroughly examine the possible modes of calculation, noisy dummy data were generated using both the classical, first-order PRV model (PRV(1)) and the proposed, second-order model (PRV(2)). Thus, pseudo-data obtained from simulations were compared to published experimental data. We observed that the second-order model, PRV(2), produces a lower variability, allowing improved K precision. Moreover, the obtained K(PRV(2)) values are very close to those obtained by classical equilibrium headspace analysis (EHSA). The PRV(2) model we propose responds to the demand for a simple, reliable method and is a useful alternative for the calculation of liquid-vapour partition coefficients.
Asunto(s)
Volatilización , Gases/química , Modelos Teóricos , Agua/químicaRESUMEN
BACKGROUND: The replacement of fat by thickeners in fat-free yogurts leads to an important modification of aroma compound partitioning, with an impact on aroma perception. Investigation of retention/release equilibria allows a good understanding of aroma compound behaviour depending on food composition. RESULTS: Vapour/liquid equilibria of ten aroma compounds (two esters, two ketones, three aldehydes and three alcohols) in several media were studied to investigate the influence of pectin addition to fat-free dairy gel on the retention/release equilibrium. The partition coefficient of each aroma compound was measured by headspace analysis at equilibrium in six media (pure water, low-methoxylated pectin gels and dairy gels with or without added pectin). The release of aroma compounds was similar in the aqueous media (pure water and pectin gels) on the one hand and in the dairy gels on the other hand. However, a trend to greater release occurred with the addition of pectin in both cases. Four aroma compounds were more retained in dairy gels than in water and pectin gels. No relationship appeared between retention and either the chemical function or hydrophobicity (logP values) for the entire set. However, several subsets showed a linear correlation between K and logP values. CONCLUSION: These results suggest that other structural properties than hydrophobicity are probably involved, changing the retention/release behaviour of aroma compounds according to the matrix composition. In order to probe the interactions, further experiments with a larger set of aroma compounds followed by molecular modelling interpretation are needed.
Asunto(s)
Productos Lácteos/análisis , Grasas de la Dieta/análisis , Compuestos Orgánicos Volátiles/química , Geles , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Pectinas/química , Transición de Fase , Compuestos Orgánicos Volátiles/administración & dosificaciónRESUMEN
Thermodynamic parameters (T, DeltaH degrees , DeltaS degrees , K) were collected from the literature and/or calculated for five esters, four ketones, two aldehydes, and three alcohols, pure compounds and compounds in aqueous solution. Examination of correlations between these parameters and the range values of DeltaH degrees and DeltaS degrees puts forward the key roles of enthalpy for vaporization of pure compounds and of entropy in liquid-vapor equilibrium of compounds in aqueous solution. A structure-property relationship (SPR) study was performed using molecular descriptors on aroma compounds to better understand their vaporization behavior. In addition to the role of polarity for vapor-liquid equilibrium of compounds in aqueous solution, the structure-property study points out the role of chain length and branching, illustrated by the correlation between the connectivity index CHI-V-1 and the difference between T and log K for vaporization of pure compounds and compounds in aqueous solution. Moreover, examination of the esters' enthalpy values allowed a probable conformation adopted by ethyl octanoate in aqueous solution to be proposed.
Asunto(s)
Compuestos Orgánicos/química , Termodinámica , Estructura Molecular , Solubilidad , VolatilizaciónRESUMEN
Perception of thousands of odors by a few hundreds of olfactory receptors (ORs) results from a combinatorial coding, in which one OR recognizes multiple odorants and an odorant is recognized by a specific group of ORs. Moreover, odorants could act both as agonists or antagonists depending on the OR. This dual agonist-antagonist combinatorial coding is in good agreement with behavioral and psychophysical observations of mixture perception. We previously described the odorant repertoire of a human OR, OR1G1, identifying both agonists and antagonists. In this paper, we performed a 3D-quantitative structure-activity relationship (3D-QSAR) study of these ligands. We obtained a double-alignment model explaining previously reported experimental activities and permitting to predict novel agonists and antagonists for OR1G1. These model predictions were experimentally validated. Thereafter, we evaluated the statistical link between OR1G1 response to odorants, 3D-QSAR categorization of OR1G1 ligands, and their olfactory description. We demonstrated that OR1G1 recognizes a group of odorants that share both 3D structural and perceptual qualities. We hypothesized that OR1G1 contributes to the coding of waxy, fatty, and rose odors in humans.
Asunto(s)
Receptores Odorantes/química , Línea Celular , Interpretación Estadística de Datos , Humanos , Ligandos , Modelos Moleculares , Estructura Molecular , Odorantes/análisis , Estructura Terciaria de Proteína , Receptores Odorantes/agonistas , Receptores Odorantes/antagonistas & inhibidores , Relación Estructura-ActividadRESUMEN
The effects of thickeners on the headspace release of aroma compounds from a model dairy gel were investigated. Starch, pectin, and locust bean gum (LBG) were introduced separately to the fat-free dairy gel via sugar syrups. The release of nine aroma compounds was analyzed by solid-phase microextraction (SPME), and the partition coefficients of retention were calculated. For an increase in starch concentration, there was an overall decrease in aroma release. Pectin concentrations in gel higher than 0.04% caused an increase in aroma release. For LBG no major effect was observed. A quantitative structure-property relationship (QSPR) approach was used to propose which types of interactions were involved between aroma molecules and thickener macromolecules in the complex foodstuff. Twenty molecular descriptors of volatile compounds appeared to be significant in correlation with the partition coefficients of retention. The surface-weighted negatively charged partial surface area seemed to play a critical role in the behavior of aroma compound.
Asunto(s)
Industria Lechera , Aditivos Alimentarios , Geles/química , Alcoholes/análisis , Ácidos Carboxílicos/análisis , Industria de Procesamiento de Alimentos , Odorantes , Pectinas , Gomas de Plantas , AlmidónRESUMEN
We carried out a QSPR (quantitative structure-property relationships) approach to evaluate the influence of the chemical structure of aqueous matrixes over the partition coefficient between the gas phase and the matrix. The determination of the partition coefficient of flavor ingredients was performed by headspace analysis at equilibrium for both saline solution and i-carrageenan gel. Starting from an initial list of 90 descriptors, we selected 10 descriptors to perform equation generation by the GFA (genetic function approximation) method available in the Cerius2 package. The best obtained equations involve only five descriptors, which encode electronic properties of charges repartition on the molecule (Jurs-RNCS and Dipole-Z) and molecules' shapes (PMI-Y, Shadow-XY, and RadOfGyration), both for saline solution and for i-carrageenan gel. However, the best-fitting equation for carrageenan gel is obtained with a quadratic relation, suggesting that the effect of carrageenan polymers only modulates but does not change the interaction of aroma compounds with water molecules.
Asunto(s)
Carragenina/química , Aromatizantes/química , Geles/química , Odorantes , Relación Estructura-Actividad Cuantitativa , Modelos Químicos , Estructura Molecular , Cloruro de Sodio/química , ViscosidadRESUMEN
This paper reports a 3D-QSAR study using Catalyst software to explain the nature of interactions between flavor compounds and beta-lactoglobulin. A set of 35 compounds, for which dissociation constants were previously determined by affinity chromatography, was chosen. The set was divided into three subsets. An automated hypothesis generation, using HypoGen software, produced a model that made a valuable estimation of affinity and provided an explanation for the lack of correlation previously observed between the hydrophobicity of terpenes and the affinity for the protein. On the basis of these results, it appears that aroma binding to beta-lactoglobulin is caused by both hydrophobic interactions and hydrogen bonding, which plays a critical role. Catalyst appears to be a reliable tool for the application of 3D-QSAR study in aroma research.
Asunto(s)
Lactoglobulinas/química , Odorantes/análisis , Relación Estructura-Actividad Cuantitativa , Programas Informáticos , Fenómenos Químicos , Química Física , Simulación por Computador , Interacciones Farmacológicas , Enlace de Hidrógeno , Modelos Químicos , Terpenos/químicaRESUMEN
Interactions between a well-characterized protein, beta-lactoglobulin, and two flavor compounds, beta-ionone and gamma-decalactone, were studied by 2D NMR spectroscopy. NMR spectra were recorded in aqueous solution (pH 2.0, 12 mM NaCl, 10% D(2)O) under conditions such that beta-lactoglobulin is present in a monomeric state. TOCSY and NOESY spectra were recorded on the protein and the complexes between protein and ligands. The spectra of the NH-CH(alpha) region showed the cross-signals due to the coupling between N- and C-bonded protons in the polypeptide backbone. The observed chemical shift variations in the presence of ligands can be assigned to changes in the protein conformation. It appears that the side chains of several amino acids are affected by binding of gamma-decalactone point into the central cavity (Leu46, Ile56, Met107, and Gln120), whereas binding of beta-ionone affects amino acids located in a groove near the outer surface of the protein (Leu104, Tyr120, and Asp129), as illustrated by molecular visualization. This NMR study provides precise information of the location of binding and confirms the existence of two different binding sites for aroma compounds on beta-lactoglobulin, which was suggested in previous competition studies by fluorometry or affinity chromatography and by structural information obtained from infrared spectroscopy.