Ligand Docking Studies Research Articles

Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling.

The search for novel effective TAAR1 ligands continues to draw great attention due to the wide range of pharmacological applications related to TAAR1 targeting. Herein, molecular docking studies of known TAAR1 ligands, characterized by an oxazoline core, have been performed in order to identify novel promising chemo-types for the discovery of more active TAAR1 agonists. In particular, the oxazoline-based compound S18616 has been taken as a reference compound for the computational study, leading to the development of quite flat and conformationally locked ligands. The choice of a "Y-shape" conformation was suggested for the design of TAAR1 ligands, interacting with the protein cavity delimited by ASP103 and aromatic residues such as PHE186, PHE195, PHE268, and PHE267. The obtained results allowed us to preliminary in silico screen an in-house series of pyrimidinone-benzimidazoles (1a-10a) as a novel scaffold to target TAAR1. Combined ligand-based (LBCM) and structure based (SBCM) computational methods suggested the biological evaluation of compounds 1a-10a, leading to the identification of derivatives 1a-3a (hTAAR1 EC50 = 526.3-657.4 nM) as promising novel TAAR1 agonists.

In-silico screening and molecular dynamics simulation of quinazolinone derivatives as PARP1 and STAT3 dual inhibitors: a novel DML approaches

Modern cancer therapy now routinely employs the blocking of many oncoproteins or pathways. With two or more medicines, multiple inhibitions are often accomplished via DML techniques. In this study, we developed 30 quinazolinone derivatives as PARP1 and STAT3 dual inhibitors using DML methods and these compounds were tested for their dual inhibitory effect on PARP1 and STAT3 using docking, MM-GBSA, and molecular dynamics simulation investigations. The docking studies of ligands against PARP1 and STAT3 were performed using the Glide module, in silico ADMET screening was performed using the quickprob module, binding energy calculation was performed using the Prime MM-GBSA module, MD simulation was performed using the Desmond module, and atomic charges were calculated using the Jaguar module of Schrodinger suite 2019-4. Of the substances studied, the derivative 1f has a considerable gliding score. The in silico ADMET characteristics are within the approved range. PRIME MM-GB/SA was used to compute the binding free energy, and the results are substantial. To investigate the dynamic behavior of the protein-ligand complex, compound 1f was subjected to MD simulation at 100 ns. The tested chemical 1f produced the greatest results in MD simulations and MM-GBSA calculations, indicating that this ligand can inhibit more effectively. Communicated by Ramaswamy H. Sarma

Design, synthesis, characterization, spectral, chemical analysis, biological evaluation, and molecular docking studies of novel fatty Schiff base ligands and their nickel and mercury complexes

A novel two Fatty Schiff bases ligands of (N-(4-(dimethyl amino) benzylidene Dodecane, heptadecane) hydrazide and N-(4-(dimethyl amino) benzylidene) dodecane, heptadecan hydrazides and their complexes with Hg and Ni were synthesized and distinguish by1HNMR, FT-IR, spectroscopy, elemental analysis, X-ray Diffractions, thermal gravimetric analysis, and magnetic moments. In-vitro strains have been used to study their antibacterial properties. The ligands and their metal complexes have been evaluated physiologically by various bacterial and fungal strains. In the comparison of free ligands with their complexes. The latter were a more potent antibacterial agent and were more efficient against gram-positive bacteria than gram-negative bacteria. Additionally, investigations using molecular docking have been carried out to assess the ideal binding location and its inhibitory effect.

Elucidating the structural and functional prophecy of the Rv2326c gene, an ABC transporter of Mycobacterium tuberculosis H37Rv through computational approach.

Tuberculosis is a fatal disease caused by Mycobacterium tuberculosis. M. tuberculosis becoming drug-resistant day by day, necessitating to know the mechanism behind the drug resistance and how to overcome this deadly malady. Drug resistance and reduced drug bioavailability are caused by a class of transporter proteins called the ATP-binding cassette (ABC) transporters, which pump a range of medicines out of cells at the price of ATP hydrolysis. By using computational approaches, we tried to elaborate the probable function of the Rv2326c gene of M. tuberculosis, perhaps involved in drug resistance mechanism. The presence of the signature motif of ABC transporters (LSGGELQRLALAAAL and LSGGQMRRVVLAGLL) and ATP binding motif (GXXXXGKT and GXXXXGKS) in the protein sequence signifying its importance in the ATP binding and transportation of molecules. Further, this manuscript elaborated about tertiary structure and validation, functional category, localization, phosphorylation site prediction, mutational analysis of conserved motifs. Ligand docking study shows the highest affinity with ATP than GTP justified its function as an ATP binding protein. The Rv2326c protein is present in the inner membrane and working as an ATP binding protein and might be playing a dynamic role in transportation. In this study, we found that Rv2326c protein might be working as an ABC transporter by which the drugs and other molecules are imported or exported into the bacterium. As a result, the current study provides a means to better understand its normal functioning and basic biology, which can help in the development of novel therapeutic targeting approaches for Rv2326c protein.

Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF- B signaling pathways.

NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC50 value of 30μg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.

Green tea leaf constituents inhibit the formation of lysozyme amyloid aggregates: An effect of mutual interactions

Amyloidoses represent a group of pathological conditions characterized by amyloid fibrils accumulating in the form of deposits in intra- or extracellular space, leading to tissue damage. The lysozyme from hen egg-white (HEWL) is often used as a universal model protein to study the anti-amyloid effects of small molecules. The in vitro anti-amyloid activity and mutual interactions of green tea leaf constituents: (−)-epigallocatechin gallate (EGCG), (−)-epicatechin (EC), gallic acid (GA), caffeine (CF) and their equimolar mixtures were studied. The inhibition of HEWL amyloid aggregation was monitored by a Thioflavin T fluorescence assay and atomic force microscopy (AFM). The interactions of the analyzed molecules with HEWL were interpreted by ATR-FTIR and protein-small ligand docking studies. EGCG was the only substance efficiently inhibiting amyloid formation (IC50 ∼193 μM), slowing the aggregation process, reducing the number of fibrils and partially stabilizing the secondary structure of HEWL. Compared to EGCG alone, EGCG-containing mixtures displayed lower overall anti-amyloid efficacy. The decrease in efficiency results from (a) the spatial interference of GA, CF and EC with EGCG while binding to HEWL, (b) the propensity of CF to form a less active adduct with EGCG, which participates in interactions with HEWL in parallel with pure EGCG. This study confirms the importance of interaction studies, revealing the possible antagonistic behavior of molecules when combined.

N-substituted tetrahydro-beta-carboline as mu-opioid receptors ligands: in silico study; molecular docking, ADMET and molecular dynamics approach.

Manipulating intracellular signals by interaction with transmembranal G-protein-coupled receptors (GPCRs) is the way of action of more than 30% of available medicines. Designing molecules against GPCRs is most challenging due to their flexible binding orthosteric and allosteric pockets, a property that lead to different mode and extent of activation of intracellular mediators. Here, in the current study we aimed to design N-substituted tetrahydro-beta-carbolines (THβC's) targeting Mu Opioid Receptors (MORs). We performed ligand docking study for reference and designed compounds against active and inactive states of MOR, as well as the active state bound to intracellular mediator of Gi. The reference compounds include 40 known agonists and antagonists, while the designed compounds include 25,227 N-substituted THβC analogues. Out of the designed compounds, 15 compounds were comparatively having better extra precision (XP) Gscore and were analyzed for absorption, distribution, metabolism, and excretion-toxicity (ADMET) properties, drug-likness, and molecular dynamic (MD) simulation. The results showed that N-substituted tetrahydro-beta-carbolines with and without C6-methoxy group substitutions (THBC/6MTHBC) analogues of A1/B1 and A9/B9 have relatively acceptable affinity and within pocket-stability toward MOR compared to the reference compounds of morphine (agonist) and naloxone (antagonist). Moreover, the designed analogues interact with key residue within the binding pocket of Asp 147 that is reported to be involved in receptor activation. In conclusion, the designed THBC analogues represent a good starting point for designing opioid receptor ligands other than morphinan scaffold, that have good synthetic accessibility which promotes feasible structural manipulation to tailor pharmacological effects with minimal side effects.

Comparative Analysis of Antibiofilm Properties of Carbohydrate derivatives over Commercial Antibiotics

Aim: The goal is to compare the antibiofilm characteristics of carbohydrate derivatives to commercial antibiotics, and docking will be used to see how the ligand, protein, and antibiotic interact molecularly. Materials and methods: The protein structure was obtained from the PDB (protein data bank) website, while the ligand structure was obtained from the NCBI-PubChem website. The biofilm from Staphylococcus aureus (bap-c1) as a protein, gluconolactone as a ligand, and nafcillin as an antibiotic are the three different types of chemicals employed for docking. The sample size was calculated using G power with pretest power at 80% and alpha value of 0.05. The sample size per group is 10 and total sample size is 30. Docking studies of protein and ligands were performed using Auto dock software. Statistics of the interactions were analyzed using IBM SPSS software. Result: Molecular interactions revealed that nafcillin shows more affinity towards the protein compared to gluconolactone and clindamycin. The binding affinity values were compared using SPSS software, it reveals that the statistical insignificance observed between the gluconolactone and nafcillin is 0.73 and for gluconolactone and clindamycin is 0.565 Conclusion: The antibiotic nafcillin appears to be more specific and selective in its antibacterial activity against the target protein.

Comparative Analysis of Antibiofilm Properties of Fluorescein Derivatives Over Commercial Antibiotics

Aim: The study is about to compare the antibiofilm properties of Novel Fluorescein derivatives to those of commercial antibiotics, using docking to see how the ligand, protein, and antibiotic interact molecularly. Materials and methods: The 3D structures of protein and ligands were procured from the PubChem, Drug bank, and PDB databases. The sample size was calculated using G power with pretest power at 80% and alpha value of 0.05. The sample size per group is 10 and total sample size is 30. Docking studies of protein and ligands were performed using Auto dock software. Statistics of the interactions were analyzed using IBM SPSS software. Result: Protein ligand interactions revealed that fluorescein shows more binding affinity towards the protein compared to commercial antibiotics cephalexin and cephalexin monohydrate. The binding affinity values were compared using SPSS software, which reveals that the statistical insignificance observed between the fluorescein and antibiotics cephalexin and cephalexin monohydrate is 0.519 and 0.400 respectively. Conclusion: The fluorescein ligand appears to be more specific and selectively works against the target protein when compared to the antibiotics.

Comparative Analysis of Antiviral Properties of Carbohydrates Derivatives over Commercial Antiviral Drugs

Aim: The study is about to compare the antiviral properties of gluconolactone derivatives to those of commercial antiviral drugs, using docking to see how the ligand, protein, and antiviral drugs interact molecularly. Materials And Methods: The 3 Dimensional structures of protein and ligands were procured from the PubChem, Drug bank, and PDB databases. The sample size was calculated using G power with pretest power at 80% and alpha value of 0.05. The sample size per group is 10 and total sample size is 30. Docking studies of protein and ligands were performed using Auto dock software. Statistics of the interactions were analyzed using IBM SPSS software. Result: Molecular interactions revealed that Ribavirin shows more affinity towards the protein compared to gluconolactone and Phosphonoformate. The binding affinity values were compared using SPSS software, it reveals that the statistical insignificance observed between the gluconolactone and Phosphonoformate is 0.263 and for gluconolactone and Ribavirin is 0.565 Conclusion: The antiviral Ribavirin appears to be more specific and selectively works against the target protein when compared to the antivirus Phosphonoformate.

Comparative Analysis of Antibacterial Properties of Fluorescein Derivatives Over Commercial Antibiotics

Aim: The study is about to compare the antibacterial properties of Novel Fluorescein derivatives to those of commercial antibiotics, using docking to see how the ligand, protein, and antibiotic interact molecularly. Materials and Methods: The 3 Dimensional structures of protein and ligands were procured from the PubChem, Drug bank, and PDB databases. The sample size was calculated using G power with pretest power at 80% and alpha value of 0.05. The sample size per group is 10 and total sample size is 30. Docking studies of protein and ligands were performed using Auto dock software. Statistics of the interactions were analyzed using IBM SPSS software. Result: Molecular interactions revealed that Clindamycin shows more affinity towards the protein compared to fluorescein and dicloxacillin. The binding affinity values were compared using SPSS software, it reveals that the statistical insignificance observed between the fluorescein and clindamycin is 0.363 and for fluorescein and dicloxacillin is 0.468 Conclusion: Antibiotic clindamycin appears to be more specific and selectively work against the target protein when compared to the dicloxacillin and fluorescein ligands.

3D-QSAR, E-pharmacophore and molecular docking to explore substituted sulfonamides as carbonic anhydrase inhibitors in epilepsy

Background- A series of aromatic sulfonamides incorporating coumarin as a lead were designed a for epilepsy target. Carbonic anhydrase is an influential target for the expansion of lead to treat epilepsy. Experimentally known carbonic anhydrase determents were identified to develop ligand based pharmacophore for anticonvulsant model. The X-ray crystallographic make-up of carbonic anhydrases with several inhibitors were utilized to develop ten energy optimized structure based (E- pharmacophore model). Pharmacophore matched candidates were utilized for docking to reclaim hits with scaffolds. The molecules having diverse structures, high docking score and low binding energy for various crystal structures of carbonic anhydrase were selected as final hits (leads). DFT is utilized to get electronic features of hits. The docking study of ligands by discovery studio had helped to establish binding interactions. The known carbonic anhydrase was reused for the development of pharmacophore hypothesis DHHRR. Based on Insilco process we came across structurally diverse hits as noncompetitive carbonic anhydrase inhibitors with better ADME. The best three hits 4, 6 and 17 were nontoxic and were selective carbonic anhydrase inhibitors with the IC50 values respectively (IC50 2.01, 2.59, 2.469). The study describes that the combined pharmacophore appeal to identify various hits which have good binding affinity for the active site of enzyme in all feasible bioactive conformations.

Protein interactions, molecular docking, antimicrobial and antifungal studies of terpyridine ligands

Resistance to antibiotics/antibacterials/antifungals in pathogenic microbes has been developing over the past few decades and has recently become a commonplace public-health peril. Thus, alternative nontoxic potent antibiotic agents are covertly needed to control antibiotic-resistant outbreaks. In an effort to combat the challenges posed by the co-occurrence of multidrug resistance, two terpyridine ligands 4′-(4-N,N′-dimethylaminophenyl)-2,2′:6′,2″-terpyridine (L1) and 4′-(4-tolyl)-2,2′:6′,2″-terpyridine (L2) have been designed, prepared and confirmed their structure by spectral studies. Thereafter, antimicrobial assay was performed against gram positive and negative bacterial strains along with fungal strains. Both compounds L1 and L2 exhibited remarkable inhibitory activities against bacteria, Escherichia coli and Staphylococcus aureus at MIC values 6.25 and 3.125 µg/ml, respectively. In addition, in silico molecular docking studies were ascertained with bacterial DNA gyrase and fungal demethylase. Furthermore, both L1 and L2 could bind Bovine Serum Albumin (BSA) protein and binding interaction has been studied with the help of UV-Visible and fluorescence spectroscopy. While fluorescence of BSA unperturbed in the presence of L2, an addition of L1 to the solution of BSA resulted significant quenching. The binding constant calculations at different temperature confirmed that the fluorescence quenching between BSA and L1 is predominantly static in nature. The toxicity of L1 and L2 was checked using Drosophila melanogaster. The toxicity analysis suggest both the dyes are non-cytotoxic in nature. Communicated by Ramaswamy H. Sarma

Toward more potent imidazopyridine inhibitors of Candida albicans Bdf1: Modeling the role of structural waters in selective ligand binding.

Novel agents to treat invasive fungal infections are urgently needed because the small number of established targets in pathogenic fungi makes the existing drug repertoire particularly vulnerable to the emergence of resistant strains. Recently, we reported that Candida albicans Bdf1, a bromodomain and extra-terminal domain (BET) bromodomain with paired acetyl-lysine (AcK) binding sites (BD1 and BD2) is essential for fungal cell growth and that an imidazopyridine (1) binds to BD2 with selectivity versus both BD1 and human BET bromodomains. Bromodomain binding pockets contain a conserved array of structural waters. Molecular dynamics simulations now reveal that one water molecule is less tightly bound to BD2 than to BD1, explaining the site selectivity of 1. This insight is useful in the performance of ligand docking studies to guide design of more effective Bdf1 inhibitors, as illustrated by the design of 10 new imidazopyridine BD2 ligands 1a-j, for which experimental binding and site selectivity data are presented.

In Silico Ligand Docking Approaches to Characterise the Binding of Known Allosteric Modulators to the Glucagon-Like Peptide 1 Receptor and Prediction of ADME/Tox Properties

The glucagon-like peptide 1 receptor (GLP-1R) is a member of the family (or class) B G-protein-coupled receptor (GPCR). The receptor is a regulator of insulin and a key target in treating Type 2 diabetes mellitus. In this investigation, computational chemistry techniques such as molecular docking were combined with in silico ADME/Tox predictions to determine the position and structure of the allosteric binding site, as well as to examine how the allosteric modulators bind to the binding site. In silico evaluation was used to evaluate the ADME/Tox properties of the allosteric modulators. The findings of the ligand docking studies suggest that the allosteric binding site is situated around the transmembrane (TM) domain TM 6 of the receptor in the active state. ADME/Tox characterisation of the allosteric modulators demonstrate that compounds 1–3 (2,6,7-trichloro-3-(trifluoromethyl)quinoxaline, 1-(5-(4-(tert-butyl)phenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-3-(methylsulfonyl)-6,7-dihydrobenzo[c]thiophen-4(5H)-one, 2-((4-chlorophenyl)thio)-3-(trifluoromethyl)quinoxaline, respectively) complied with the traditional method of evaluating drug-likeness; Lipinski’s rule of 5. The allosteric modulator compound 4 (3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)phenyl cyclohexanecarboxylate) failed to comply with Lipinski’s rule of five as a result of having a logP value of over 5.6. Moreover, molecular docking studies provide insights into potential allosteric binding sites and possible interactions. Finally, the in silico ADME/Tox study results are described as relevant to developing a viable drug candidate.

In Silico Prediction of the Metabolic Resistance of Vitamin D Analogs against CYP3A4 Metabolizing Enzyme.

The microsomal cytochrome P450 3A4 (CYP3A4) and mitochondrial cytochrome P450 24A1 (CYP24A1) hydroxylating enzymes both metabolize vitamin D and its analogs. The three-dimensional (3D) structure of the full-length native human CYP3A4 has been solved, but the respective structure of the main vitamin D hydroxylating CYP24A1 enzyme is unknown. The structures of recombinant CYP24A1 enzymes have been solved; however, from studies of the vitamin D receptor, the use of a truncated protein for docking studies of ligands led to incorrect results. As the structure of the native CYP3A4 protein is known, we performed rigid docking supported by molecular dynamic simulation using CYP3A4 to predict the metabolic conversion of analogs of 1,25-dihydroxyvitamin D2 (1,25D2). This is highly important to the design of novel vitamin D-based drug candidates of reasonable metabolic stability as CYP3A4 metabolizes ca. 50% of the drug substances. The use of the 3D structure data of human CYP3A4 has allowed us to explain the substantial differences in the metabolic conversion of the side-chain geometric analogs of 1,25D2. The calculated free enthalpy of the binding of an analog of 1,25D2 to CYP3A4 agreed with the experimentally observed conversion of the analog by CYP24A1. The metabolic conversion of an analog of 1,25D2 to the main vitamin D hydroxylating enzyme CYP24A1, of unknown 3D structure, can be explained by the binding strength of the analog to the known 3D structure of the CYP3A4 enzyme.

Chemical speciation, antioxidant activity and molecular docking of copper(II) complexes with pyridinedicarboxylic acids and different ligands of low molecular mass

ABSTRACT Analyses of potentiometric measurements were conducted on ternary complexes of copper(II) with dipicolinic acid and quinolinic acid, as well as lactic acid, oxalic acid, citric acid, and phosphoric acid, which are components of blood plasma. Studies on chemical speciation showed that ternary compounds were more likely to be formed. In systems with quinolinic acid, the solubility was small, and most complexes precipitated at pH ≤ 2. In situ isolated ternary and binary complexes of CuDiPic(H2O)2 were evaluated for antioxidant activity, as shown by their inhibiting activity of superoxide anion (O2.−), which demonstrates copper(II) complexes provide protective effects. Docking studies of ligands with a protein kinase revealed that the Cu(II) metal centre is crucial for the successful interaction of the complex with the receptor’s active site.

Schiff-base ligands containing phenanthroline terminals: Synthesis, characterization, biological activities and molecular docking study

Three new phenanthroline-derived ligands were synthesized by the Schiff base condensation method. The first ligand was the result of 1,10-phenanthroline-2-carboxyaldehyde reaction with 1,4-diaminobutane (L1). The other ligands were obtained 1,6-diaminohexane (L2) and 1,8-diaminooctane (L3) with the phenanthroline aldehyde in separate reactions. The structures of all ligands were elucidated using spectral techniques such as FT-IR, 13C NMR, 1H NMR and LC ESI/MS. The geometric properties of ligands such as bond lengths, bond angles, dihedral angles, electronic properties, HOMO and LUMO energies were calculated by using the Gaussian 09w programme. Ligands were optimized with B3LYP and 6–311++G(2d,p) basis set and NMR and FT-IR spectra were calculated. Experimental and theoretical spectrum data were compared. All of the ligands showed antibacterial activity against Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. The anticancer activities of the ligands were also determined against human breast cancer (MCF7) and prostate cancer (DU145) cell lines. In addition, which conformation of the ligands was determined by the theoretical calculations. Docking studies of ligands with bovine serum albumin (BSA) were performed using Autock Tools 1.5.6 programme.

Mapping the Binding Sites of UDP and Prostaglandin E2 Glyceryl Ester in the Nucleotide Receptor P2Y6.

Cyclooxygenase‐2 catalyzes the biosynthesis of prostaglandins from arachidonic acid and the biosynthesis of prostaglandin glycerol esters (PG‐Gs) from 2‐arachidonoylglycerol. PG‐Gs are mediators of several biological actions such as macrophage activation, hyperalgesia, synaptic plasticity, and intraocular pressure. Recently, the human UDP receptor P2Y6 was identified as a target for the prostaglandin E2 glycerol ester (PGE2‐G). Here, we show that UDP and PGE2‐G are evolutionary conserved endogenous agonists at vertebrate P2Y6 orthologs. Using sequence comparison of P2Y6 orthologs, homology modeling, and ligand docking studies, we proposed several receptor positions participating in agonist binding. Site‐directed mutagenesis and functional analysis of these P2Y6 mutants revealed that both UDP and PGE2‐G share in parts one ligand‐binding site. Thus, the convergent signaling of these two chemically very different agonists has already been manifested in the evolutionary design of the ligand‐binding pocket.

An Expanded Survey of the Moth PBP/GOBP Clade in Bombyx mori: New Insight into Expression and Functional Roles.

We studied the expression profile and ontogeny (from the egg stage through the larval stages and pupal stages, to the elderly adult age) of four OBPs from the silkworm moth Bombyx mori. We first showed that male responsiveness to female sex pheromone in the silkworm moth B. mori does not depend on age variation; whereas the expression of BmorPBP1, BmorPBP2, BmorGOBP1, and BmorGOBP2 varies with age. The expression profile analysis revealed that the studied OBPs are expressed in non-olfactory tissues at different developmental stages. In addition, we tested the effect of insecticide exposure on the expression of the four OBPs studied. Exposure to a toxic macrolide insecticide endectocide molecule (abamectin) led to the modulated expression of all four genes in different tissues. The higher expression of OBPs was detected in metabolic tissues, such as the thorax, gut, and fat body. All these data strongly suggest some alternative functions for these proteins other than olfaction. Finally, we carried out ligand docking studies and reported that PBP1 and GOBP2 have the capacity of binding vitamin K1 and multiple different vitamins.