| 1. |
- Tu, Guangde, et al.
(författare)
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Core electron chemical shifts of hydrogen-bonded structures
- 2009
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Ingår i: Chemical Physics Letters. - Amsterdam : Elsevier BV. - 0009-2614 .- 1873-4448. ; 468:4-6, s. 294-298
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Tidskriftsartikel (refereegranskat)abstract
- We examine the possibility to study hydrogen-bonded structures through core ionization energies. We use a recently derived self-interaction corrected density functional theory method where the core ionization energies for all chemically shifted elements are obtained by a single calculation of the ground state of the structures. A direct dependency between the hydrogen atom to acceptor atom bond length and the chemical shift of the core ionization energy of the acceptor atom is found, something that has rami. cations for the possibility of effective predictions of hydrogen bond lengths in hydrogen-bonded systems. This observation is verified by the conventional, much more time-consuming, self-consistent field calculations based on density functional theory.
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| 2. |
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| 3. |
- Brown, Christian, et al.
(författare)
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Structural and functional characterization of the microtubule interacting and trafficking domains of two oomycete chitin synthases
- 2016
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 283:16, s. 3072-3088
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Tidskriftsartikel (refereegranskat)abstract
- Chitin synthases (Chs) are responsible for the synthesis of chitin, a key structural cell wall polysaccharide in many organisms. They are essential for growth in certain oomycete species, some of which are pathogenic to diverse higher organisms. Recently, a Microtubule Interacting and Trafficking (MIT) domain, which is not found in any fungal Chs, has been identified in some oomycete Chs proteins. Based on experimental data relating to the binding specificity of other eukaryotic MIT domains, there was speculation that this domain may be involved in the intracellular trafficking of Chs proteins. However, there is currently no evidence for this or any other function for the MIT domain in these enzymes. To attempt to elucidate their function, MIT domains from two Chs enzymes from the oomycete Saprolegnia monoica were cloned, expressed and characterized. Both were shown to interact strongly with the plasma membrane component phosphatidic acid, and to have additional putative interactions with proteins thought to be involved in protein transport and localization. Aiding our understanding of these data, the structure of the first MIT domain from a carbohydrate-active enzyme (MIT1) was solved by NMR, and a model structure of a second MIT domain (MIT2) was built by homology modelling. Our results suggest a potential function for these MIT domains in the intracellular transport and/or regulation of Chs enzymes in the oomycetes.
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| 4. |
- Cheng, J., et al.
(författare)
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Molecular switches of the κ opioid receptor triggered by 6′-GNTI and 5′-GNTI
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The κ opioid receptor (κOR) is a member of G-protein-coupled receptors, and is considered as a promising drug target for treating neurological diseases. κOR selective 6′-GNTI was proved to be a G-protein biased agonist, whereas 5′-GNTI acts as an antagonist. To investigate the molecular mechanism of how these two ligands induce different behaviors of the receptor, we built two systems containing the 5′-GNTI-κOR complex and the 6′-GNTI-κOR complex, respectively, and performed molecular dynamics simulations of the two systems. We observe that transmembrane (TM) helix 6 of the κOR rotates about 4.6° on average in the κOR-6′-GNTI complex. Detailed analyses of the simulation results indicate that E2976.58 and I2946.55 play crucial roles in the rotation of TM6. In the simulation of the κOR-5′-GNTI system, it is revealed that 5′-GNTI can stabilize TM6 in the inactive state form. In addition, the kink of TM7 is stabilized by a hydrogen bond between S3247.47 and the residue V691.42 on TM1.
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| 5. |
- Feng, Yanli, et al.
(författare)
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A supramolecular photoswitch constructed by intermolecular hydrogen bond between BTEPy and TTF-COOH
- 2008
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 455:4-6, s. 256-260
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Tidskriftsartikel (refereegranskat)abstract
- A novel supramolecular photoswitch containing bisthienylethene- pyridine (BTEPy) and carboxyl attached tetrathiafluvalene (TTF-COOH) was constructed via intermolecular hydrogen bond. FT-IR spectra, XPS characterizations, H-1 NMR and theoretical calculation were carried out to verify the formation of the intermolecular hydrogen bond. The supramolecular self-assemblies BTEPy 2TTF show good photo-chromic properties. A molecular switch with UV/vis light as inputs and electrochemical signals as outputs was obtained.
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| 6. |
- Fu, Y., et al.
(författare)
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Defect-Assisted Loading and Docking Conformations of Pharmaceuticals in Metal–Organic Frameworks
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:14, s. 7719-7727
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Tidskriftsartikel (refereegranskat)abstract
- Understanding of drug–carrier interactions is essential for the design and application of metal–organic framework (MOF)-based drug-delivery systems, and such drug–carrier interactions can be fundamentally different for MOFs with or without defects. Herein, we reveal that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host–guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites, and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOFs without defects, the loading capacity is greatly reduced. We employed solid-state NMR spectroscopy and molecular simulations to elucidate the drug–carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects were revealed.
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| 7. |
- Fu, Yao, et al.
(författare)
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Duet of Acetate and Water at the Defects of Metal-Organic Frameworks
- 2019
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 19:3, s. 1618-1624
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Tidskriftsartikel (refereegranskat)abstract
- Metal-organic frameworks (MOFs) are porous crystalline materials with promising applications in molecular adsorption, separation, and catalysis. It has been discovered recently that structural defects introduced unintentionally or by design could have a significant impact on their properties. However, the exact chemical composition and structural evolution under different conditions at the defects are still under debate. In this study, we performed multidimensional solid-state nuclear magnetic resonance (SSNMR) coupled with computer simulations to elucidate an important scenario of MOF defects, uncovering the dynamic interplay between residual acetate and water. Acetate, as a defect modulator, and water, as a byproduct, are prevalent defect-associated species, which are among the key factors determining the reactivity and stability of defects. We discovered that acetate molecules coordinate to a single metal site monodentately and pair with water at the neighboring position. The acetates are highly flexible, which undergo fast libration as well as a slow kinetic exchange with water through dynamic hydrogen bonds. The dynamic processes under variable temperatures and different hydration levels have been quantitatively analyzed across a broad time scale from microseconds to seconds. The integration of SSNMR and computer simulations allows a precision probe into defective MOF structures with intrinsic dynamics and disorder.
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| 8. |
- Gao, Li, et al.
(författare)
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A mechanistic hypothesis for the cytochrome P450-catalyzed cis-trans isomerization of 4-hydroxytamoxifen : an unusual redox reaction
- 2011
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 51:9, s. 2293-2301
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Tidskriftsartikel (refereegranskat)abstract
- We provide a detailed description of the cis-trans isomerization of 4-hydroxytamoxifen/endoxifen catalyzed by several isoforms from the cytochrome P450 (CYP) superfamily, including CYP1B1, CYP2B6, and CYP2C19. We show that the reactions mainly involve redox processes catalyzed by CYP, DFT calculation results strongly suggest that the isomerization occurs via a cationic intermediate. The cationic cis-isomer is more than 3 kcal/mol more stable than the trans form, resulting in an easier conversion from trans-to-cis than cis-to-trans. The cis-trans isomerization is a rarely reported CYP reaction and is ascribed to the lack of a second abstractable proton on the ethenyl group of the triarylvinyl class of substrates. The cationic intermediates thus formed instead of the stable dehydrogenation products allow for isomerization to occur. As a comparison, the reactions for the tamoxifen derivatives are compared to those of other substrates, 4-hydroxyacetanilide and raloxifene, for which the stable dehydrogenation products are formed.
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| 9. |
- Gao, Li, et al.
(författare)
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Characterization of Agonist Binding to His524 in the Estrogen Receptor alpha Ligand Binding Domain
- 2012
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 116:16, s. 4823-4830
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Tidskriftsartikel (refereegranskat)abstract
- The bioactivities of the natural steroidal estrogen 17 beta-estradiol (E-2), the synthetic estrogen diethylstilbestrol (DES), and the phytoestrogen genistein (GEN) are intimately associated with their binding to the estrogen receptor alpha ligand binding domain (ER alpha LBD) and accordingly allostery. Molecular modeling techniques have been performed on agonists in complex with the LBD, focusing on the pivotal role of His524 modeled as the epsilon-tautomer and the protonated form (depending on pH). It is found that E-2 binds to the active LBD with the aid of Leu525, showing existing stable patterns of an H-binding network with Glu419 via His524 in all models. The main difference seen in the effect is that the full agonists E-2 and DES have higher binding energies to the protonated His524 than the partial agonists GEN and Way-169916 (W), which is in line with noted experimental transcriptional activities. In conclusion, the study demonstrates that the phytoestrogen GEN interacts differently with the LBD than what E-2 and DES do, which explains the observed signaling differences.
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| 10. |
- Gao, Li, et al.
(författare)
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Conformational enantiomerization and estrogen receptor alpha binding of anti-cancer drug tamoxifen and its derivatives
- 2011
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 51:2, s. 306-314
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Tidskriftsartikel (refereegranskat)abstract
- The anticancer drug tamoxifen (TAM) displays two chiral vinyl propeller structures, which interconvert so rapidly that the process is undetectable on the NMR time scale. In the present work, the enantiomerization processes were investigated with molecular modeling techniques. The threshold mechanisms probed at the different rings were shown to be identical, i.e., involving a synchronous three-ring flip, with a correlated rotation of the rings. In order to reveal the pharmacological profiles of the two chiral forms, we performed structural studies on the ligand binding domain of estrogen receptor alpha. (ER alpha LBD) and associated ligands. The enantiomers, with opposite torsional twist, were found to be discriminated by ER alpha. For TAM and its main metabolites, the effects of the stereoselectivity of ER alpha are overcome by the low energy cost for helical inversion between the two torsional enantiomers, estimated to be similar to 3 kcal/mol.
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