Design of novel SHP2 inhibitors using Topomer CoMFA, HQSAR analysis, and molecular docking

Tong, Jianbo; Luo, Ding; Zhang, Xing; Bian, Shuai

doi:10.1007/s11224-020-01677-8

Cited by 11 publications

(3 citation statements)

References 38 publications

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“…The higher the scoring function value of Total-score, the better the affinity between the small molecule ligand extracted from the macromolecular protein and the receptor; the closer the absolute value of Crash is to zero, the smaller the degree of inappropriateness between the ligand and the receptor extracted from the macromolecular protein. Polar is the score of the polarity function, which can be divided into binding sites located on the surface (the higher the score, the better) and the interior of the molecule (the lower the score, the better) [40] . When the Total-score is greater than 5.0, the output posture is excellent.…”

Section: Resultsmentioning

confidence: 99%

Molecular design, molecular docking and ADMET study of cyclic sulfonamide derivatives as SARS-CoV-2 inhibitors

Tong

Zhang

Luo

et al. 2021

Chinese Journal of Analytical Chemistry

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Section: Resultsmentioning

confidence: 99%

Molecular design, molecular docking and ADMET study of cyclic sulfonamide derivatives as SARS-CoV-2 inhibitors

Tong

Zhang

Luo

et al. 2021

Chinese Journal of Analytical Chemistry

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“…According to the rule of SYBYL 2.0, Total‐Score (output data) reflects the binding affinity between a ligand and protein (Li et al, 2019). In general, the interaction between protein and ligand is stable for Total‐Score values higher than 5 (Tong et al, 2021). Our docking calculations showed that the binding affinity of COR to ZmPIP2;5 (Total‐Score = 5.9756) was better than that of MeJA to ZmPIP2;5 (Total‐Score = 4.8187).…”

Section: Discussionmentioning

confidence: 99%

Coronatine promotes maize water uptake by directly binding to the aquaporin ZmPIP2;5 and enhancing its activity

Wang

et al. 2023

JIPB

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Water uptake is crucial for crop growth and development and drought stress tolerance. The water channel aquaporins (AQP) play important roles in plant water uptake. Here, we discovered that a jasmonic acid analog, coronatine (COR), enhanced maize (Zea mays) root water uptake capacity under artificial water deficiency conditions. COR treatment induced the expression of the AQP gene Plasma membrane intrinsic protein 2;5 (ZmPIP2;5). In vivo and in vitro experiments indicated that COR also directly acts on ZmPIP2;5 to improve water uptake in maize and Xenopus oocytes. The leaf water potential and hydraulic conductivity of roots growing under hyperosmotic conditions were higher in ZmPIP2;5‐overexpression lines and lower in the zmpip2;5 knockout mutant, compared to wild‐type plants. Based on a comparison between ZmPIP2;5 and other PIP2s, we predicted that COR may bind to the functional site in loop E of ZmPIP2;5. We confirmed this prediction by surface plasmon resonance technology and a microscale thermophoresis assay, and showed that deleting the binding motif greatly reduced COR binding. We identified the N241 residue as the COR‐specific binding site, which may activate the channel of the AQP tetramer and increase water transport activity, which may facilitate water uptake under hyperosmotic stress.

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“…In addition, under the Tripos force field the Powell conjugate gradient minimization algorithm minimized the potential energies of the compounds. The energy convergence criterion was 0.005 kcal/mol Å with the maximum number of iterations at 1000 [27] . The IC 50 values were all converted to pIC 50 (-LogIC 50 ) and added to the spreadsheet as compound variables.…”

Section: Methodsmentioning

confidence: 99%

Computational strategies towards developing novel SARS-CoV-2 Mpro inhibitors against COVID-19

Luo

Tong

Zhang

et al. 2022

Journal of Molecular Structure

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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be a serious threat due to the lack of a specific therapeutic agent. Computational methods are particularly suitable for rapidly fight against SARS-CoV-2. This present research aims to systematically explore the interaction mechanism of a series of novel bicycloproline-containing SARS-CoV-2 M pro inhibitors through integrated computational approaches. We designed six structurally modified novel SARS-CoV-2 M pro inhibitors based on the QSAR study. The four designed compounds with higher docking scores were further explored through molecular docking, molecular dynamics (MD) simulations, free energy calculations, and residual energy contributions estimated by the MM-PBSA approach, with comparison to compound 23(PDB entry 7D3I). This research not only provides robust QSAR models as valuable screening tools for the development of anti-COVID-19 drugs, but also proposes the newly designed SARS-CoV-2 M pro inhibitors with nanomolar activities that can be potentially used for further characterization to treat SARS-CoV-2 virus.

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Design of novel SHP2 inhibitors using Topomer CoMFA, HQSAR analysis, and molecular docking

Cited by 11 publications

References 38 publications

Molecular design, molecular docking and ADMET study of cyclic sulfonamide derivatives as SARS-CoV-2 inhibitors

Molecular design, molecular docking and ADMET study of cyclic sulfonamide derivatives as SARS-CoV-2 inhibitors

Coronatine promotes maize water uptake by directly binding to the aquaporin ZmPIP2;5 and enhancing its activity

Computational strategies towards developing novel SARS-CoV-2 Mpro inhibitors against COVID-19

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