Dietary intervention with a low glycemic index and full nutritional support is emerging as an effective strategy for diabetes management. Here, we found that the treatment of a novel compound dietary fiber and high-grade protein diet (CFP) improved glycemic control and insulin resistance in streptozotocin-induced diabetic mice, with a similar effect to liraglutide. In addition, CFP treatment ameliorated diabetes-related metabolic syndromes, such as hyperlipidemia, hepatic lipid accumulation and adipogenesis, systemic inflammation, and diabetes-related kidney damage. These results were greatly associated with enhanced gut barrier function and altered gut microbiota composition and function, especially those bacteria, microbial functions, and metabolites related to amino acid metabolism. Importantly, no adverse effect of CFP was found in our study, and CFP exerted a wider arrange of protection against diabetes than liraglutide. Thereby, fortification with balanced dietary fiber and high-grade protein, like CFP, might be an effective strategy for the management and treatment of diabetes.

There are many kinds of mucins in the mucus of the digestive tract, which are usually glycosylated.The mucin side chain sugar groups play many roles, such as bacteria adhesion, colonization and immunological regulation.Fucose is an important sugar group in the mucin side chains.This paper reviewed the roles of fucose acting as adhesion sites, signaling molecules and regulating intestinal functions.

To investigate the effects of dietary replacement of fish-soy oil mixtures by palm oil on growth performance, feed utilization, muscular fatty acid composition, morphological index and liver tissue structure of yellow catfish (Pel-teobagrus vachelli Richardson), five iso-proteic (400 g/kg), iso-lipidic (100 g/kg) and iso-energetic (15.70 MJ/kg) diets were formulated, in which the control group was supplemented with 1:2 fish-soy oil mixtures, and trial groups adopted different palm oil level (10 g/kg, 25 g/kg, 40 g/kg and 55 g/kg) to replace the mixture oil, respectively. For a 8-week trial. The results showed that dietary palm oil replacement had no significant effect on the feed intake, body weight, growth rate, feed efficiency, and protein retention efficiency (P>0.05). All the above parameters were increased with in-creasing dietary palm oil replacement level up to 25 g/kg, and then decreased. LA and n-3 HUFA concentrations in dorsal muscle significantly decreased with increasing dietary palm oil replacement level (P<0.05), while muscular n-3/n-6 significantly increased with increasing dietary palm oil replacement level (P<0.05). Furthermore, there were no significant difference in condition factor and viscerosomatic index among different groups (P>0.05). However, hepato-somatic index of 55 g/kg palm oil group was significantly higher than that of 25 g/kg palm oil group (P<0.05). The swelling hepatocytes with nuclei displacement and the increasing number of hepatic sinusoid and lipid cells were ob-served in 55 g/kg palm oil group. In conclusion, palm oil that replace 1:2 fish-soy oil mixtures up to 25 g/kg had no sig-nificant effect on the growth performance but improved the fatty acid profile of dorsal muscle.

Oral administration of Clostridium butyricum as probiotics is increasingly gaining importance in the treatment of intestinal inflammations and improvement of animal performance. The mechanisms of host cell receptor recognition of C. butyricum and downstream immune signaling pathways leading to this beneficial event, however, remain unclear. In this study, C. butyricum was investigated for its capability to influence the innate immune response of HT-29 cells to explore its mechanism of action. Our data showed that C. butyricum was able to stimulate toll-like receptor 2 (TLR2) production at mRNA level; however, TLR4, TLR5, TLR9, and myeloid differentiation primary response protein 88 (MyD88) transcription levels remain unaltered. The nuclear factor B (NF-B), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-) levels in response to C. butyricum were significantly increased, indicating that HT-29 cells were sensitised by C. butyricum. It is the first time that our findings have showed the specific signaling pathways in HT-29 cells stimulated by C. butyricum, which, at least in part, can help to explain the beneficial properties of C. butyricum.

Glutamine has an essential role with a beneficial function in improving the nutrition status of young mammals. The influence of L-Glutamine (GM) on the Coefficient of Total Tract Apparent Digestibility (CTTAD) and Apparent Ileal Digestibility (AID), the jejunal enzyme activity associated with nutrient absorption and the energy production in weaned piglets has not been sufficiently studied. The aim of the present study is to provide a profile of the effects of Gln on CTTAD, AID, the activities of jejunal enzymes in connection with nutrient digestion and absorption and energy production. The piglets were weaned at 21 days of age. There were two groups in Experiment 1 and 2 representing supplementation with 0 or 1% Gln to the basal diet. In Experiment 1, the CTTAD of the dietary components and energy was assessed at 3, 5, 10, 15 and 30 days after weaning. In Experiment 2, productive performance, AID, jejunal enzyme activities and expression of Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma) were measured at 10 and 30 days post-weaning. Results showed that dietary Gln supplementation significantly improved the CTTAD of DM, OM, GE and AA and the CTTAD increased significantly with the extension of days after weaning. For the entire experiment, the average daily gain increased by 12.40% (p = 0.049) in the Gin group. Dietary Gln supplementation increased the AID of GE, Leu, Lys, Cys and Pro by 12.50 (p = 0.047), 7.03% (p = 0.041), 5.95% (p = 0.036), 9.30 (p = 0.025), 11.17% (p = 0.009), respectively at 10 days post-weaning; Pro by 6.11% (p = 0.044) at 30 days post-weaning. Jejunal brush border membrane-bound alkaline phosphatase activity increased in the Gln-supplemented pigs by 30.36% (p = 0.048) and 6.21% (p = 0.30) at 10 and 30 days post-weaning, respectively. Compared with the control pigs, the mRNA level of PPAR gamma decreased by 10.85% (p = 0.14) and 41.88% (p = 0.023) after the administration of 1% Gln for 10 and 30 days, respectively. The activity of glutamine synthetase decreased by 48.89% (p = 0.044) at 10 days post-weaning and pyruvate kinase by 13.13% (p = 0.036) at 30 days post-weaning in the Gln-supplemented pigs. In conclusion, 1% Gln supplementation to the post-weaned piglet diet enhanced the CTTAD and AID of diet, improved intestinal absorption and modified jejunal enzyme activities related to Gin metabolism and energy production.

The beneficial effects of Clostridium butyricum in the treatment of intestinal inflammatory disorders are well known. However, it is not fully understood how such bacteria inhibit pathogen-induced intestinal diseases. For this purpose, we investigated the effects of C. butyricum and its spent culture supernatants (SCS) on Escherichia coli (EHEC) growth and adherence to chicken embryo intestinal cells (CEICs). We also evaluated the potential of C. butyricum to inhibit EHEC-induced apoptosis in CEICs. C. butyricum and its SCS exhibited significant inhibitory activity on EHEC growth and adherence to CEICs. C. butyricum also showed a significant inhibitory effect on EHEC-induced apoptosis by modulating the expression of XIAP (X-linked inhibitor of apoptosis protein), BclXL (B-cell lymphoma-extra large), FAS, Bcl2 (B-cell leukemia/lymphoma-2), BAX (Bcl-2-associated X protein), P53 (Tumor protein 53) and via inhibition of caspase-9 and caspase-3 activation. These results together indicate that C. butyricum possesses the ability to prevent EHEC-induced intestinal disorders both directly, through inhibiting EHEC viability, and indirectly, via medicating EHEC-induced apoptosis. These observations may help explain the beneficial properties of C. butyricum. Furthermore, our data is novel in the case of poultry and the manner in which C. butyricum prevents the EHEC-induced apoptosis provides supportive information for the treatment of colibacillosis in poultry.

A novel metabolomic method based on gas chromatography-mass spectrometry was applied to investigate serum metabolites in response to dietary Gln supplementation in piglets. Sixteen, 21-d-old pigs were weaned and assigned randomly to 2 isonitrogenous diets: 1) Gln diet, which contained 1% L-Gln (as-fed basis), and 2) control diet, which contained L-Ala to make this diet isonitrogenous with the Gln diet. Serum samples were collected to characterize metabolites after a 30-d treatment. in addition, 4 liver samples per treatment were collected to examine enzyme activity and gene expression involved in metabolic regulation. Results indicated that 12 metabolites were altered (P < 0.05) by Gln treatment, including carbohydrates, AA, and fatty acids. A leave-one-out cross validation of random forest analysis indicated that Pro was most important among the 12 metabolites. Thus, these data demonstrate that the control and Gln-supplemented pigs differed (P < 0.05) in terms of metabolism of carbohydrates, Pro, Tyr, and glycerophospholipids. Principal component analysis yielded separate clusters of profiles between the Gln and control groups. Metabolic enzyme activities of Ala aminotransferase and hexokinase increased by 26.8% (P = 0.026) and 26.2% (P = 0.004) in the liver of Gln-supplemented pigs vs. control, respectively, whereas pyruvate kinase (PK) activity decreased by 29.1% (P = 0.001). The gene expression of PK in the liver decreased by 66.1% (P = 0.034) by Gln treatment for 30 d. No differences were observed for the mRNA abundance of mammalian target of rapamycin and PPARγ. On the basis of these data, Gln treatment affected carbohydrate, lipid, and AA metabolism in the whole body of the early weaned piglets. These findings provide insight into specific metabolic pathways and lay the groundwork for the complex metabolic alteration in response to dietary Gln supplementation of pigs.

A novel metabolomic method based on gas chromatography/mass spectrometry (GC-MS) was applied to determine the metabolites in the serum of piglets in response to weaning and dietary L-glutamine (Gln) supplementation. Thirty-six 21-d-old piglets were randomly assigned into three groups. One group continued to suckle from the sows (suckling group), whereas the other two groups were weaned and their diets were supplemented with 1% (w/w) Gln or isonitrogenous L-alanine, respectively, representing Gln group or control group. Serum samples were collected to characterize metabolites after a 7-d treatment. Results showed that twenty metabolites were down-regulated significantly (P<0.05) in control piglets compared with suckling ones. These data demonstrated that early weaning causes a wide range of metabolic changes across arginine and proline metabolism, aminosugar and nucleotide metabolism, galactose metabolism, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acid, and fatty acid metabolism. Dietary Gln supplementation increased the levels of creatinine, D-xylose, 2-hydroxybutyric acid, palmitelaidic acid, and α-L-galactofuranose (P<0.05) in early weaned piglets, and were involved in the arginine and proline metabolism, carbohydrate metabolism, and fatty acid metabolism. A leave-one-out cross-validation of random forest analysis indicated that creatinine was the most important metabolite among the three groups. Notably, the concentration of creatinine in control piglets was decreased (P=0.00001) compared to the suckling piglets, and increased (P=0.0003) in Gln-supplemented piglets. A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways, leading to the abnormality of carbohydrate metabolism, amino acid metabolism, and lipid metabolism, which could be partially improved by dietary Gln supplementation. These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.

Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase that requires two cofactor Mg(2+) ions for catalysis in regulating many important cellular signals. Experimentally, Li(+) is a competitive inhibitor of GSK3β relative to Mg(2+), while this mechanism is not experienced with other group I metal ions. Herein, we use native Mg(2)(2+)-Mg(1)(2+) GSK3β and its Mg(2)(2+)-M(1)(+) (M = Li, Na, K, and Rb) derivatives to investigate the effect of metal ion substitution on the mechanism of inhibition through two-layer ONIOM-based quantum mechanics/molecular mechanics (QM/MM) calculations and molecular dynamics (MD) simulations. The results of ONIOM calculations elucidate that the interaction of Na(+), K(+), and Rb(+) with ATP is weaker compared to that of Mg(2+) and Li(+) with ATP, and the critical triphosphate moiety of ATP undergoes a large conformational change in the Na(+), K(+), and Rb(+) substituted systems. As a result, the three metal ions (Na(+), K(+), and Rb(+)) are not stable and depart from the active site, while Mg(2+) and Li(+) can stabilize in the active site, evident in MD simulations. Comparisons of Mg(2)(2+)-Mg(1)(2+) and Mg(2)(2+)-Li(1)(+) systems reveal that the inline phosphor-transfer of ATP and the two conserved hydrogen bonds between Lys85 and ATP, together with the electrostatic potential at the Li(1)(+) site, are disrupted in the Mg(2)(2+)-Li(1)(+) system. These computational results highlight the possible mechanism why Li(+) inhibits GSK3β.

GPR40 is a novel potential target for the treatment of type 2 diabetes. In this work, a two-layered ONIOM based QM/MM approach was employed to study the interactions between GW9508 and GPR40: wild-type, H86F, and H137F mutated systems. The calculated results clearly indicated that His137 is directly involved in ligand recognition through the NH–π interaction with the GW9508. In contrast, His86 is not interacting with the GW9508 in the NH–π interaction. The interaction energies, calculated at the MP2/6–31(d, p) level, were performed to gain more insight into the energetic differences of the wild-type and two mutated systems at the atomistic level. In addition, the obtained pharmacophore model was well consistent with structure–functional requirements for the binding of GPR40 agonists and with per-residue energy decomposition of the ONIOM calculations.

Notice of Retraction After careful and considered review of the content of this paper by a duly constituted expert committee, this paper has been found to be in violation of IEEE's Publication Principles. We hereby retract the content of this paper. Reasonable effort should be made to remove all past references to this paper. The presenting author of this paper has the option to appeal this decision by contacting TPII@ieee.org. This study was designed to develop a culture system from the stromal-vascular fraction of chicken adipose tissue that can be used to investigate the function of leptin receptor (Ob-R) in regulating the deposition of adipose tissues. Abdominal adipose tissue was excised from 10-day-old male broilers (Gallus domesticus) by sterile dissection. The stromal-vascular cell fraction from the adipose tissue was isolated by collagenase digestion, filtration, and subsequent centrifugation. These preadipocytes were seeded in six well culture plates and proliferated to confluency in 10% bovine serum in DMEM/F12 medium. Three small interference RNAs (siRNAs) were synthesized to interfere the Ob-R gene expression in chicken adipocytes. Real-time PCR was used to check the expression of Ob-R gene after interference. The suppression rate of the three siRNAs was 61.5%, 61.8% and 21.9% respectively compared to the control group (P<;0.05). The Ob-R-1 and Ob-R-2 siRNAs can successfully decrease the expression of Ob-R gene.

Inhibition of the interactions between the tumor suppressor protein p53 and its negative regulators, the MDM2 and MDMX oncogenic proteins, is increasingly gaining interest in cancer therapy and drug design. In this study, we carry out molecular docking, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann and generalized Born/surface area (MM-PB/GBSA) binding free energy calculations on an active compound 3a and an inactive compound NC-1, which share a common pyrrolopyrimidine-based scaffold. MD simulations and MM-PB/GBSA calculations show that the compound NC-1 may not bind to MDM2 and MDMX, in agreement with the experimental results. Detailed MM-PB/GBSA calculations on the MDM2-3a and MDMX-3a complexes unravel that the binding free energies are similar for the two complexes. Furthermore, the van der Waals energy is the largest component of the binding free energy for both complexes, which indicates that the interactions between the compound 3a and MDM2 and MDMX are dominated by shape complementarity. In addition, the analysis of individual residue contribution and protein-ligand binding mode show that the three functional groups on R₁, R₂, and R₃ of the compound 3a can mimic the spatial orientation of the side chains of Phe19, Trp23, and Leu26 of p53, respectively. The obtained computational results suggest that the compound 3a can act as a dual inhibitor of MDM2-p53 and MDMX-p53 interactions, consistent with the experimental results.

As a serine/threonine protein kinase, glycogen synthase kinase 3β (GSK3β) is an essential component of several cellular processes, including insulin, growth factor, and Wnt signaling. The conserved K85 is important to GSK3β activity and FRATide binding. To elucidate the mechanisms concerning kinase inactivation and nonbinding of FRATide to GSK3β, molecular dynamics (MD) simulation, molecular mechanics generalized Born/surface area (MM_GBSA) calculation, and normal mode analysis (NMA) were performed on both the wild-type (WT) and the K85M mutation of the GSK3β-FRATide complex. The results revealed that the periodic open-closed conformational change of the G loop, together with the compact conformation of the RD pocket, was disturbed in the K85M mutant, in contrast to those in the WT. This in turn caused inhibition of GSK3β. Specifically, the correct folding pattern of GSK3β was disrupted in the K85M mutant, resulting in the loss of two key hydrogen bonds between K214 of FRATide and E290 and K292 of GSK3β, respectively. Furthermore, MM_GBSA calculations indicated that the K85M mutation could lead to a less energy-favorable GSK3β-FRATide complex. In addition, NMA demonstrated that the "rocking" of the N- and C-terminal domains of GSK3β, which coordinates the mutual movement of both lobes, inducing the opening and closing of the active site of GSK3β, which may assist the entry of ATP into the ATP binding site and the release of the ADP product. Strikingly, this phenomenon was not clearly observed in the K85M mutation. This study provides a structural basis for the effect of the K85M mutation on the GSK3β-FRATide complex.

Substrate specificity of protein kinases is of fundamental importance for the integrity and fidelity of signaling pathways. Glycogen synthase kinase 3β (GSK3β) has a unique substrate specificity that prefers phosphorylation of its substrates at the P+4 serine before it can further phosphorylate the substrate at the P0 serine in the canonical motif SXXXS(p), where S(p) is the primed phosphorylation site. The detailed phosphorylation mechanism, however, is not clearly understood. In this study, a three-dimensional (3D) model of the ternary complex of GSK3β, ATP, and the phosphorylated glycogen synthase (pGS), termed GSK3β/ATP/pGS, is constructed using a hierarchical approach and by integrating molecular modeling and molecular dynamics (MD) simulations. Based on the 3D model, the substrate primed phosphorylation mechanism is investigated via two 12 ns comparative MD simulations of the GSK3β/ATP/pGS and GSK3β/ATP/GS systems, which differ in the phosphate group bound to the P+4 serine of GS. In agreement with structural analysis, computed binding free energies reveal that the binding of pGS to GSK3β is favored in the prephosphorylated state compared with the GS native state. More importantly, comparison with the system simulated without primed phosphorylation in the GSK3β/ATP/GS complex shows that for an optimal phosphorylation reaction to occur, the pGS priming phosphate in the GSK3β/ATP/pGS system optimizes the proper orientation of the GSK3β N- and C-terminal domains and clamps the P0 serine of pGS in the appropriate configuration for interaction with the ATP γ-phosphate within the catalytic groove.

AbstractThe Fe(III)‐catalyzed addition of indole derivatives towards enamides can afford either mono‐ (III) or bisadducts (VII) depending on the amount of indole used.

We investigated the effects of crossbreeding on slaughter traits and the chemical composition of chicken breast muscle. Trials were conducted using 120 broilers from four lines: Xiao-Shan chicken (XS), Xian-Ju chicken (XJ), Xiao-Shan chicken♂♂ × Xian-Ju chicken♀♀ (Zhenan 1, ZNY1) and Xiao-Shan chicken♂♂ × (Guang-Xi Yellow chicken♂♂×Xian-Ju chicken♀♀) ♀♀ (Zhenan 2, ZNY2). The birds were slaughtered at 120 days of age and the slaughter traits were measured. Breast muscles were sampled to determine chemical composition. The slaughter traits of hybrid chickens were improved. Both hybrid strains had higher intramuscular fat (IMF) and inosine-5'-monophosphate (inosinic acid, IMP). Concentrations of monounsaturated fatty acids (MUFA) in breast muscles from the two hybrids were significantly higher than in the other two breeds (p < 0.05). The concentration of polyunsaturated fatty acids (PUFA) in the breast muscles of the two hybrids was significantly lower than in the other two breeds (p < 0.05). ZNY2 had significantly lower (p < 0.05) concentrations of myristic acid (C14:0). The breast muscle of ZNY1 had significantly higher palmitic acid (C16:0) concentrations than XS, XJ, or ZNY2 (p < 0.05). The concentrations of oleic acid (C18:1) and eicosapentaenoic acid (C20:5n-3, EPA) in breast muscle from the two hybrid lines were significantly higher than the other two breeds (p < 0.05). Breast muscles from XS and XJ chickens contained significantly higher docosahexenoic acid (C22:6n-3, DHA) than the two hybrid lines (p < 0.05). The XS and XJ chickens had lower n-6/n-3 ratios than the two hybrids (p < 0.05). Breast muscles from ZNY1 and ZNY2 contained higher concentrations of essential amino acids (p < 0.05), total amino acids (p < 0.05), and some individual amino acids (p < 0.05). In conclusion, crossbreeding improved the slaughter traits of chickens and increased intramuscular fat and inosinic acid content in breast muscle. The fatty acid and amino acid compositions of breast muscles were also improved by crossbreeding.

The role of water molecules is increasingly gaining interest in drug design, and several studies have highlighted their paramount contributions to the specificity and the affinity of ligand binding. In this study, we employ the two‐layer ONIOM‐based quantum mechanics/molecular mechanics (QM/MM) calculations, molecular dynamics (MD) simulations, and molecular docking studies to investigate the effect of bridging water molecules at the GSK3β‐inhibitors interfaces. The results obtained from the ONIOM geometry optimization and AIM analysis corroborated the presence of bridging water molecules that form hydrogen bonds with protein side chain of Thr138 and/or backbone of Gln185, and mediate interactions with inhibitors in the 10 selected GSK3β‐inhibitor complexes. Subsequently, MD simulations carried out on a representative system of 1R0E demonstrated that the bridging water molecule is stable at the GSK3β‐inhibitor interface and appears to contribute to the stability of the protein–inhibitor interactions. Furthermore, molecular docking studies of GSK3β‐inhibitor complexes indicated that the inhibitors can increase binding affinities and the better docked conformation of inhibitors can be obtained by inclusion of the bridging water molecules, especially for the flexible inhibitors, in docking experiments into individual protein conformations. Our results elucidate the importance of bridging water molecules at the GSK3β‐inhibitor interfaces and suggest that they might prove useful in rational drug design. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011

Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine protein kinase that is involved in several biological processes including insulin and Wnt signaling pathways. The Wnt signaling via FRAT-mediated displacement of axin inhibits GSK3β activity toward non-primed substrates without affecting its activity toward primed substrates. Herein, molecular dynamics simulation, molecular mechanics generalized Born/surface area (MM_GBSA) calculation, and normal mode analysis are performed to explore the structural influence of the double mutations K214/A–E215/Q of FRATide on the GSK3β–FRATide complex. The results reveal that the priming phosphate-binding site, the primed substrate-binding site, the alignment of the critical active site residues in the ATP-binding site, as well as the periodic open–closed conformational change of the ATP-binding site, which are critical for the catalytic activity of GSK3β, are negligibly influenced in the mutated system compared with the wild-type (WT) system. This indicates that FRATide does not inhibit the GSK3β activity toward primed substrates. Additionally, MM_GBSA calculation indicates that the less energy-favorable GSK3β–FRATide complex is observed in the mutant than in the WT complex.

A simple layer-by-layer (LBL) assembly strategy was established for constructing a novel reagentless biosensor based on a nanocomposite of methylene blue multiwalled carbon nanotubes (MB-MWNTs). A nanocomposite of MB-MWNTs was obtained by direct premixing and possessed good dispersion in barbital-HCl buffer. Through electrostatic interactions, the nanocomposite of MB-MWNI's could alternately be assembled with horseradish peroxidase (HRP) on the An electrode modified with precursor films. UV/Vis spectra and scanning electron microscopy (SEM) were applied to reveal the formation of the nanocomposite of MB-MWNTs. The LBL assembly process was also verified by electrochemical impedance spectroscopy (EIS). The MB is a well-established mediator and efficiently facilitated the electron shuttle between the HRP and the electrode, as demonstrated by the cyclic voltammetry (CV) measurements. The as-prepared reagentless biosensor exhibited a fast response for the determination of hydrogen peroxide (H2O2) and reached 95% of the steady-state current within 3 s. It was found that the linear response range of the reagentless biosensor for H2O2 was from 4.0 mu M to 3.78 mM with a detection limit of 1.0 mu M and a sensitivity of 22.5 mu A mM(-1). The biosensor exhibited a high reproducibility and stability.

Halogen–water–hydrogen bridges (XWH bridges), in which one hydrogen bond (H-bond) in a traditional water-mediated H-bond bridge is replaced by a halogen bond (X-bond), is a novel mode of interaction for water in biological molecules. In this study, we investigate several protein–halogenated ligand complexes using a two-layer quantum mechanics/molecular mechanics (QM/MM) ONIOM method. Analysis of the geometric characteristics and energy behaviors of the complexes, together with the AIM results, indicate that XWH bridges are present in these systems. Furthermore, our investigations show that XWH bridges can have an important role in ligand recognition and binding.