Characterization the performances of twofold resveratrol integrated compounds in binding with SIRT1 by molecular dynamics simulation and molecular mechanics/generalized born surface area (MM/GBSA) calculation

Shi, Shanshan; Wang, Qiudan; Liu, Sai; Qu, Zhiyuan; Li, Kaihang; Geng, Xiaoju; Wang, Tao; Gao, Jian

doi:10.1016/j.chemphys.2021.111108

Cited by 13 publications

(5 citation statements)

References 24 publications

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“…To calculate the binding free energies of the c-Myc-G4/ ligand complexes, MM/GBSA calculation was conducted with the reported calculation Equation (Chen et al, 2019b;Shi et al, 2021). To investigate the detailed binding interactions between c-Myc-G4 and stabilizers, MM/GBSA free energy decomposition analysis was carried out using the mmpbsa module in Amber12 (Rehman & Khan, 2019).…”

Section: Simulation and Mm/gbsa Free Energy Calculationmentioning

confidence: 99%

Structure‐based discovery of Licoflavone B and Ginkgetin targeting c‐Myc G‐quadruplex to suppress c‐Myc transcription and myeloma growth

et al. 2022

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G‐quadruplex (G4), present in the c‐Myc promoter, has emerged as an attractive cancer‐specific molecular target for drug development. So, the discovery of small molecules to stabilize c‐Myc‐G4 to inhibit transcription of c‐Myc protein is of great significance. Herein, a combined molecular docking‐based virtual screening strategy, molecular dynamics (MD) simulation, and molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculation was conducted on the existing L6000 Natural Compound Library. Four natural compounds, including Licoflavone B, Demethyleneberberine, Ginkgetin, and Mulberroside C, were predicted to have preferable binding affinities to c‐Myc G4 and then selected for commercial purchase and experimental evaluation. Compounds Licoflavone B and Ginkgetin can significantly inhibit myeloma cell proliferation, with IC50 values <8 μM against the RPMI‐8226 cell line. Moreover, our data demonstrated that the two compounds could simultaneously downregulate c‐Myc transcription and expression. Collectively, compounds Licoflavone B and Ginkgetin might be regarded as new candidates for the development of the more potent c‐Myc‐G4 stabilizers in the future.

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Section: Simulation and Mm/gbsa Free Energy Calculationmentioning

confidence: 99%

Structure‐based discovery of Licoflavone B and Ginkgetin targeting c‐Myc G‐quadruplex to suppress c‐Myc transcription and myeloma growth

et al. 2022

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“…Before MD simulation, energy minimization was performed using the sander module of Amber18 (Chen, Wang, Gao, et al., 2019). This involved optimizing all water molecules and Cl − ions through a limited all‐atoms approach for receptor proteins and ligands via a 2500‐step steepest descent followed by a 2500‐step conjugate gradient method (Chen et al., 2018; Shi et al., 2021). Subsequently, side chains, ligands, water molecules, and amino acid ions underwent optimization through an additional 5000 steps before unconstrained optimization with another round of steepest descent followed by conjugate gradient methods over another set of 5000 steps.…”

Section: Methodsmentioning

confidence: 99%

“…The binding free energies of the c‐Maf/ligand complexes were calculated using the MM/GBSA method, employing the established calculation equation (Dai et al., 2022; Gao et al., 2022; Qu et al., 2021; Shi et al., 2021). To gain insights into the intricate binding interactions between c‐Maf and inhibitors, a comprehensive analysis of MM/GBSA free energy decomposition was performed utilizing the mmpbsa module in Amber 18 (Chen et al., 2016; Hou et al., 2011).…”

Section: Methodsmentioning

confidence: 99%

Discovery of small molecule c‐Maf inhibitors using molecular docking‐based virtual screening, molecular dynamics simulation, and biological evaluation

Hu,

Zeng,

Zhang

et al. 2023

Chem Biol Drug Des

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Multiple myeloma (MM) is a prevalent plasma cell malignancy in the blood system that remains incurable. Given the abnormally high expression of c‐Maf in most MM patients, targeting c‐Maf presents an attractive therapeutic approach for treating MM malignancies. In this study, we employed a combined strategy involving molecular docking‐based virtual screening, molecular dynamics (MD) simulation, and molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculation on existing FDA‐approved drugs. Six compounds were selected for further experimental assay: vemurafenib, sorafenib, sildenafil, fluvastatin, erlotinib, and glimepiride. Among these compounds, sorafenib and glimepiride exhibited significant inhibition of myeloma cell proliferation in the RPMI‐8226 cell line. Moreover, both compounds simultaneously downregulated c‐Maf protein expression to induce G1 phase arrest and apoptosis in myeloma cells. Collectively, sorafenib and glimepiride may be considered promising candidates for developing more potent c‐Maf inhibitors in the future.

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“…With the aim of calculating the binding free energy, the calculation of MM/GBSA was carried out by using MM/GBSA in AMBER 12 software via the following equation ( Kollman et al, 2000 ; Chen Q. et al, 2019 ; An et al, 2020 ; Shi et al, 2021 ) .

…”

Section: Methodsmentioning

confidence: 99%

Computational Insights Into the Effects of the R190K and N121Q Mutations on the SARS-CoV-2 Spike Complex With Biliverdin

Geng

et al. 2021

Front. Mol. Biosci.

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The SARS-CoV-2 spike has been regarded as the main target of antibody design against COVID-19. Two single-site mutations, R190K and N121Q, were deemed to weaken the binding affinity of biliverdin although the underlying molecular mechanism is still unknown. Meanwhile, the effect of the two mutations on the conformational changes of “lip” and “gate” loops was also elusive. Thus, molecular dynamics simulation and molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculation were conducted on the wild-type and two other SARS-CoV-2 spike mutants. Our simulations indicated that the R190K mutation causes Lys190 to form six hydrogen bonds, guided by Asn99 and Ile101, which brings Lys190 closer to Arg102 and Asn121, thereby weakening the interaction energy between biliverdin and Ile101 as well as Lys190. For the N121Q mutation, Gln121 still maintained a hydrogen bond with biliverdin; nevertheless, the overall binding mode deviated significantly under the reversal of the side chain of Phe175. Moreover, the two mutants would stabilize the lip loop, which would restrain the meaningful upward movement of the lip. In addition, N121Q significantly promoted the gate loop deviating to the biliverdin binding site and compressed the site. This work would be useful in understanding the dynamics binding biliverdin to the SARS-CoV-2 spike.

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Characterization the performances of twofold resveratrol integrated compounds in binding with SIRT1 by molecular dynamics simulation and molecular mechanics/generalized born surface area (MM/GBSA) calculation

Cited by 13 publications

References 24 publications

Structure‐based discovery of Licoflavone B and Ginkgetin targeting c‐Myc G‐quadruplex to suppress c‐Myc transcription and myeloma growth

Structure‐based discovery of Licoflavone B and Ginkgetin targeting c‐Myc G‐quadruplex to suppress c‐Myc transcription and myeloma growth

Discovery of small molecule c‐Maf inhibitors using molecular docking‐based virtual screening, molecular dynamics simulation, and biological evaluation

Computational Insights Into the Effects of the R190K and N121Q Mutations on the SARS-CoV-2 Spike Complex With Biliverdin

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