Assessing the performance of three resveratrol in binding with SIRT1 by molecular dynamics simulation and MM/GBSA methods: the weakest binding of resveratrol 3 to SIRT1 triggers a possibility of dissociation from its binding site

Chen, Han; Wang, Yan; Gao, Zheng; Yang, Wenzhuo; Gao, Jian

doi:10.1007/s10822-019-00193-0

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…To make it electrically neutral, an appropriate amount of K + was added to each system to replace the same number of water molecules. The sander module was used for each system's energy optimization, which is minimized by a three-step optimization method as described in the previous study (Chen et al, 2019a). After that, a gradually heated process was carried out from 0 K to 300 K over 60 ps, and the system was in an NVT ensemble.…”

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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“…The system was minimized using the conjugate gradient and steepest descent methods as described in previous papers. 54 , 55 Subsequently, the system was gradually heated from 0 to 310 K over 60 ps. Finally, a 500 ns MD simulation with a 2 fs time step was performed in triplicate for the system at a constant temperature of 310 K. Throughout all simulations the SHAKE procedure was employed to constrain all bonds involving at least one hydrogen atom, and the particle mesh Ewald (PME) method was adopted to deal with long-range electrostatic interactions.…”

Section: Methodsmentioning

confidence: 99%

Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth

Gao

Zhang

et al. 2022

Sig Transduct Target Ther

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NEMO/IKKβ complex is a central regulator of NF-κB signaling pathway, its dissociation has been considered to be an attractive therapeutic target. Herein, using a combined strategy of molecular pharmacological phenotyping, proteomics and bioinformatics analysis, Shikonin (SHK) is identified as a potential inhibitor of the IKKβ/NEMO complex. It destabilizes IKKβ/NEMO complex with IC50 of 174 nM, thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo. In addition, we also elucidated the potential target sites of SHK in the NEMO/IKKβ complex. Our study provides some new insights for the development of potent small-molecule PPI inhibitors.

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“…Appropriate numbers of K + were added to neutralize those systems. Every single system was initially energy minimized via three steps with the help of a sander module, as described in a previous study ( Chen H. et al, 2019 ). Then each system was heated gradually in the NVT ensemble from 0 to 300 K in 100 ps.…”

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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Assessing the performance of three resveratrol in binding with SIRT1 by molecular dynamics simulation and MM/GBSA methods: the weakest binding of resveratrol 3 to SIRT1 triggers a possibility of dissociation from its binding site

Cited by 15 publications

References 29 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

Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth

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

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