Ligand chirality can affect histidine protonation of vitamin-D receptor: ab initio molecular orbital calculations in water

Terauchi, Yuta; Suzuki, Rie; Takeda, Ryosuke; Kobayashi, Ittetsu; Kittaka, Atsushi; Takimoto‐Kamimura, Midori; Kurita, Noriyuki

doi:10.1016/j.jsbmb.2018.09.020

Cited by 17 publications

(10 citation statements)

References 23 publications

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“…Protonation states of the His residues in a protein can have a significant effect on specific interactions between the protein and a ligand [23] , as such the relevant protonation states were assigned to His residues based on the pKa value predicted by the PROPKA3.1 program [24] . His residues, which possessed a pKa value higher than 6 and were located on the surface of RORγt, were assigned a Hip + protonation, whereas the His residues with a lower pKa value and located inside the RORγt structure were assigned Hie or Hid protonation.…”

Section: Details Of Molecular Simulationsmentioning

confidence: 99%

Structural change of retinoic-acid receptor-related orphan receptor induced by binding of inverse-agonist: Molecular dynamics and ab initio molecular orbital simulations

Suzuki

Nakamura

Saito

et al. 2020

Computational and Structural Biotechnology Journal

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Section: Details Of Molecular Simulationsmentioning

confidence: 99%

Structural change of retinoic-acid receptor-related orphan receptor induced by binding of inverse-agonist: Molecular dynamics and ab initio molecular orbital simulations

Suzuki

Nakamura

Saito

et al. 2020

Computational and Structural Biotechnology Journal

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“…We and newly calculated and collected more than 13 600 FMO calculation data sets ,,− including data sets for 1418 unique PDB entries in collaboration with the FMO Drug Design Consortium (FMODD), which was established for the application of computational science such as FMO calculation to drug discovery. Using these data, we constructed the FMODB, which is a treasure trove of quantitative inter- and intramolecular interaction energies in biomolecular systems that will be useful for a wide range of applications in many life science research fields related to drug discovery and structural biology, including the study of molecular recognition.…”

Section: Introductionmentioning

confidence: 99%

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

Takaya

Watanabe

Nagase

et al. 2021

J. Chem. Inf. Model.

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We developed the world's first web-based public database for the storage, management, and sharing of fragment molecular orbital (FMO) calculation data sets describing the complex interactions between biomacromolecules, named FMO Database (https://drugdesign.riken.jp/FMODB/). Each entry in the database contains relevant background information on how the data was compiled as well as the total energy of each molecular system and interfragment interaction energy (IFIE) and pair interaction energy decomposition analysis (PIEDA) values. Currently, the database contains more than 13 600 FMO calculation data sets, and a comprehensive search function implemented at the front-end. The procedure for selecting target proteins, preprocessing the experimental structures, construction of the database, and details of the database front-end were described. Then, we demonstrated a use of the FMODB by comparing IFIE value distributions of hydrogen bond, ion-pair, and XH/π interactions obtained by FMO method to those by molecular mechanics approach. From the comparison, the statistical analysis of the data provided standard reference values for the three types of interactions that will be useful for determining whether each interaction in a given system is relatively strong or weak compared to the interactions contained within the data in the FMODB. In the final part, we demonstrate the use of the database to examine the contribution of halogen atoms to the binding affinity between human cathepsin L and its inhibitors. We found that the electrostatic term derived by PIEDA greatly correlated with the binding affinities of the halogen containing cathepsin L inhibitors, indicating the importance of QM calculation for quantitative analysis of halogen interactions. Thus, the FMO calculation data in FMODB will be useful for conducting statistical analyses to drug discovery, for conducting molecular recognition studies in structural biology, and for other studies involving quantum mechanics-based interactions.

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“…The Dell Precision T3500 workstation (Dell) (Ubuntu 18.04 LTS, Intel Xeon W3680 3.33 GHz CPU (6 core), 23.5 GB RAM) was used for the FMO calculation. The binding energy between ERRγ-LBD and BPA-monoF was estimated from the total energies using the following equation …”

Section: Methodsmentioning

confidence: 99%

“…The binding energy between ERRγ-LBD and BPA-monoF was estimated from the total energies using the following equation. 51 binding energy total energy (BPA monoF/ERR LBD complex) total energy (the energy minimized BPA monoF) total energy(apo ERR LBD)…”

Section: ■ Experimental Proceduresmentioning

confidence: 99%

Evaluation of the Influence of Halogenation on the Binding of Bisphenol A to the Estrogen-Related Receptor γ

Suyama

Kaneko

Kesamaru

et al. 2020

Chem. Res. Toxicol.

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Halogenation of organic compounds is one the most important transformations in chemical synthesis and is used for the production of various industrial products. A variety of halogenated bisphenol analogs have recently been developed and are used as alternatives to bisphenol A (BPA), which is a raw material of polycarbonate that has adverse effects in animals. However, limited information is available on the potential toxicity of the halogenated BPA analogs. In the present study, to assess the latent toxicity of halogenated BPA analogs, we evaluated the binding and transcriptional activities of halogenated BPA analogs to the estrogen-related receptor γ (ERRγ), a nuclear receptor that contributes to the growth of nerves and sexual glands. Fluorinated BPA analogs demonstrated strong ERRγ binding potency, and inverse antagonistic activity, similar to BPA. X-ray crystallography and fragment molecular orbital (FMO) calculation revealed that a fluorine-substituted BPA analog could interact with several amino acid residues of ERRγ-LBD, strengthening the binding affinity of the analogs. The ERRγ binding affinity and transcriptional activity of the halogenated BPAs decreased with the increase in the size and number of halogen atom(s). The IC50 values, determined by the competitive binding assay, correlated well with the binding energy obtained from the docking calculation, suggesting that the docking calculation could correctly estimate the ERRγ binding potency of the BPA analogs. These results confirmed that ERRγ has a ligand binding pocket that fits very well to BPA. Furthermore, this study showed that the binding affinity of the BPA analogs can be predicted by the docking calculation, indicating the importance of the calculation method in the risk assessment of halogenated compounds.

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Ligand chirality can affect histidine protonation of vitamin-D receptor: ab initio molecular orbital calculations in water

Cited by 17 publications

References 23 publications

Structural change of retinoic-acid receptor-related orphan receptor induced by binding of inverse-agonist: Molecular dynamics and ab initio molecular orbital simulations

Structural change of retinoic-acid receptor-related orphan receptor induced by binding of inverse-agonist: Molecular dynamics and ab initio molecular orbital simulations

FMODB: The World’s First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

Evaluation of the Influence of Halogenation on the Binding of Bisphenol A to the Estrogen-Related Receptor γ

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