Theoretical investigations on the effects of mutations in important residues of NS1B on its RNA-binding using molecular dynamics simulations

Xu, Dan; Zheng, Qing‐Chuan

doi:10.1016/j.compbiomed.2022.105412

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…The MM/GBSA approach ( Srinivasan et al, 1998 ; Lee et al, 2004 ) was used to calculate the binding free energies between curcumin and human SIK3. The MM/GBSA method has been widely employed to evaluate the binding affinities between ligands and enzyme ( Tse and Verkhivker, 2015 ; Wang et al, 2017 ; Chen Q. Q. et al, 2019 ; Shi and Xu, 2019 ; Wei et al, 2019 ; Xu and Zheng, 2022 ). Previously, the MM/GBSA framework has been detailly introduced ( Honig and Nicholls, 1995 ; Genheden and Ryde, 2015 ; Onufriev and Case, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

et al. 2023

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Natural products are widely used for treating mitochondrial dysfunction-related diseases and cancers. Curcumin, a well-known natural product, can be potentially used to treat cancer. Human salt-induced kinase 3 (SIK3) is one of the target proteins for curcumin. However, the interactions between curcumin and human SIK3 have not yet been investigated in detail. In this study, we studied the binding models for the interactions between curcumin and human SIK3 using computational tools such as homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations. The open activity loop conformation of SIK3 with the ketoenol form of curcumin was the optimal binding model. The I72, V80, A93, Y144, A145, and L195 residues played a key role for curcumin binding with human SIK3. The interactions between curcumin and human SIK3 were also investigated using the kinase assay. Moreover, curcumin exhibited an IC50 (half-maximal inhibitory concentration) value of 131 nM, and it showed significant antiproliferative activities of 9.62 ± 0.33 µM and 72.37 ± 0.37 µM against the MCF-7 and MDA-MB-23 cell lines, respectively. This study provides detailed information on the binding of curcumin with human SIK3 and may facilitate the design of novel salt-inducible kinases inhibitors.

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Section: Methodsmentioning

confidence: 99%

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

et al. 2023

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“…The MM/GBSA approach , was used to calculate the binding free energies of ABBV-075 and ABBV-744 binding with BRD4-BD1 or BRD4-BD2. The MM/GBSA method is usually used to quantify the binding affinities between small molecules and their target. − The MM/GBSA framework has been described in detail in previous studies. − In the present study, the MM/GBSA approach was applied to calculate the energy terms over 1000 frames from the last 100 ns of the MD simulation for the inhibitor/BRD4 complex systems. Additionally, the entropy was calculated via the statistical average with 100 frames in the last 100 ns MS simulation.…”

Section: Methodsmentioning

confidence: 99%

Selectivity Mechanism of Pyrrolopyridone Analogues Targeting Bromodomain 2 of Bromodomain-Containing Protein 4 from Molecular Dynamics Simulations

Shi,

Zheng,

Zhou

et al. 2023

ACS Omega

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Bromodomain and extra-terminal domain (BET) proteins play an important role in epigenetic regulation and are linked to several diseases; therefore, they are interesting targets. BET has two bromodomains: bromodomain 1 (BD1) and BD2. Selective targeting of BD1 or BD2 may produce different activities and greater effects than pan-BD inhibitors. However, the selective mechanism of the specific core must be studied at the atomic level. This study determined the effectiveness of pyrrolopyridone analogues to selectively inhibit BD2 using a pan-BD inhibitor (ABBV-075) and a selective-BD2 inhibitor (ABBV-744). Molecular dynamics simulations and calculations of binding free energies were used to systematically study the selectivity of BD2 inhibition by the pyrrolopyridone analogues. Overall, the pyrrolopyridone analogue inhibitors targeting BD2 interacted mainly with the following amino acid pairs between bromodomain-containing protein 4 (BRD4)-BD1 and BRD4-BD2 complexes: I146/V439, N140/N433, D144/H437, P82/P375, V87/V380, D88/D381, and Y139/Y432. The pyrrolopyridone analogues targeting BRD4-BD2 were divided into five regions based on selectivity mechanism. These results suggest that the R3 and R5 regions of pyrrolopyridone analogues can be modified to improve the selectivity between BRD4-BD1 and BRD4-BD2. The selectivity of BD2 inhibition by pyrrolopyridone analogues can be used to design novel BD2 inhibitors based on a pyrrolopyridone core.

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“…Apart from the challenges in modeling protein-RNA interactions, additional challenges remain in studying protein-RNA complex structures, including the fact that the interaction involves dynamics of biomolecules involved, both with respect to the RNA (which may also include modified RNAs), as well as with respect to the protein [107] . Nevertheless, the predicted complex structures from these computational modeling methods (such as template-based docking) can serve as a starting point for simulations to provide critical insights on modeled protein-RNA interactions with respect to refining such complexes, as well as to study their dynamics and provide an in-depth biophysical investigation of the complex with structural and energetic analysis [115] , [116] , [117] , [118] , [119] , [120] , [121] .…”

Section: Computational Advancements Accelerating the Study Of Epitran...mentioning

confidence: 99%

Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain

Miller,

Demny,

Tamamis

et al. 2023

Computational and Structural Biotechnology Journal

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Theoretical investigations on the effects of mutations in important residues of NS1B on its RNA-binding using molecular dynamics simulations

Cited by 4 publications

References 49 publications

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

Selectivity Mechanism of Pyrrolopyridone Analogues Targeting Bromodomain 2 of Bromodomain-Containing Protein 4 from Molecular Dynamics Simulations

Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain

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