PADFrag: A Database Built for the Exploration of Bioactive Fragment Space for Drug Discovery

Yang, Jing‐Fang; Wang, Fan; Jiang, Wen; Zhou, Guangyou; Li, Chengzhang; Zhu, Xiaolei; Hao, Ge‐Fei; Yang, Guang‐Fu

doi:10.1021/acs.jcim.8b00285

Cited by 46 publications

(44 citation statements)

References 32 publications

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“…Typically they are based on molecular dynamics simulations of the receptor-ligand complex. These approaches are used to estimate the free energy of binding small ligands to biological macromolecules [17][18][19][20][21]30]. Typically they are based on molecular dynamics simulations of the receptor-ligand complex.…”

Section: Resultsmentioning

confidence: 99%

“…Due to the importance of MM/PBSA and MM/GBSA approaches, the binding free energies were calculated using two different programs, 1) a program developed by Wang [17], which is based on MM/PB(GB)SA approach and 2) ACFIS (ACFIS 2.0) a computer-aided fragmentbased drug discovery (FBDD) web server [18][19][20][21].…”

Section: Resultsmentioning

confidence: 99%

“…Secondly the free energy of the binding of the investigated molecules to COVID-19 M pro and spike glycoprotein (ΔG) were calculated both with MM/PBSA {ΔG(PB)} and MM/GBSA {ΔG(GB)} methods using ACFIS 2.0 web server [18][19][20][21]…”

Section: Resultsmentioning

confidence: 99%

“…Molecular docking studies were performed on the identified active sites [16], using AutoDock-Vina software. The binding free energies of the most stable ligandprotein systems that determined by molecular docking analysis, were calculated by the programs developed by Wang [17] and the ACFIS 2.0 web server [18][19][20][21].…”

Section: Methods and Calculationsmentioning

confidence: 99%

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Interactions mechanism of commonly used drugs for the treatment of Covid-19

Çeli̇k¹,

DEMİRAG²,

Özel³

et al. 2021

Bull. Chem. Soc. Eth.

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In this study conformation analysis of seven drugs commonly used in the treatment of COVID-19 was performed. The most stable conformers of the drug molecules were used as initial data for docking analysis. Using the Cavityplus program, the probable most active binding sites of both apo and holo forms of COVID-19 main protease enzyme (Mpro) and spike glycoprotein of SARSCoV-2 receptors were determined. The interaction mechanisms of the 7 FDA approved drugs (arbidol, colchicine, dexamethasone, favipiravir, galidesivir, hydroxychloroquine, remdesivir) were examined using the AutoDock Vina program. The six of the seven drugs were found to be more stable in binding to apo form of COVID-19 Mpro and spike glycoprotein. Moreover, a set of molecular mechanics (MM) Poisson-Boltzmann (PB) surface area (SA) calculations on the investigated drugs-protein systems were performed and the estimated binding free energy of remdesivir and the apo form of Mpro system was found to be the best. The interaction results of FDA drugs with the apo form of COVID-19 Mpro and spike glycoprotein can play an important role for the treatment of COVID-19. KEY WORDS: COVID-19, Drugs, Molecular modelling, Conformational analysis, Molecular docking Bull. Chem. Soc. Ethiop. 2020, 34(3), 613-623. DOI: https://dx.doi.org/10.4314/bcse.v34i3.16

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methods and Calculationsmentioning

confidence: 99%

See 2 more Smart Citations

Interactions mechanism of commonly used drugs for the treatment of Covid-19

Çeli̇k¹,

DEMİRAG²,

Özel³

et al. 2021

Bull. Chem. Soc. Eth.

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“…At the same time, a previously constructed PADFrag database (derived from commercial drugs and pesticides) was used as a fragment library. 32 Chemicals and instruments All materials and chemicals were purchased from commercial sources, including Sinopharm Chemical Reagent Co., Ltd (Beijing, China), Sigma-Aldrich (Shanghai, China), Merck (Kenilworth, USA), and J&K (Beijing, China), etc., and used without further purification. Silica gel 200-300 mesh for isolation was purchased from Qingdao Broadchem Industrial Co., Ltd (Qingdao, China…”

Section: Molecule Designmentioning

confidence: 99%

Fragment‐based discovery of flexible inhibitor targeting wild‐type acetohydroxyacid synthase and P197L mutant

Yang

Chen

et al. 2020

Pest Management Science

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BACKGROUND Intensifying weed resistance has challenged the use of existing acetohydroxyacid synthase (AHAS)‐inhibiting herbicides. Hence, there is currently an urgent requirement for the discovery of a new AHAS inhibitor to effectively control AHAS herbicide‐resistant weed species produced by target mutation. RESULTS To combat weed resistance caused by AHAS with P197L mutation, we built a structure library consisting of pyrimidinyl‐salicylic acid derivatives. Using the pharmacophore‐linked fragment virtual screening (PFVS) approach, hit compound 8 bearing 6‐phenoxymethyl substituent was identified as a potential AHAS inhibitor with antiresistance effect. Subsequently, derivatives of compound 8 were synthesized and evaluated for their inhibitory activities. The study of the enzyme‐based structure–activity relationship and structure−resistance relationship studies led to the discovery of a qualified candidate, 28. This compound not only significantly inhibited the activity of wild‐type Arabidopsis thaliana (At) AHAS and P197L mutant, but also exhibited good antiresistance properties (RF = 0.79). Notably, compared with bispyribac at 37.5–150 g of active ingredient per hectare (g a.i. ha–1), compound 27 exhibited higher growth inhibition against both sensitive and resistant Descurainia sophia, CONCLUSION The title compounds have great potential to be developed as new leads to effectively control herbicide‐resistant weeds comprising AHAS with P197L mutation. Also, our study provided a positive case for discovering novel, potent and antiresistance inhibitors using a fragment‐based drug design approach.

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Future direction of agrochemical development for plant disease in China

Guo

Song

et al. 2021

Food and Energy Security

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The current global population has reached 7.6 billion, and the per capita agricultural acreage is declining continuously, imposing a big challenge to establish fully sustainable food production systems to provide sufficient food for the growing population (Carvalho, 2017;Godfray et al., 2010;Tilman et al., 2011). However, this challenge is made more difficult by many issues, including climate change, soil environment change, resistant pests, pathogens, and weeds (Fritsche, 2018;

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PADFrag: A Database Built for the Exploration of Bioactive Fragment Space for Drug Discovery

Cited by 46 publications

References 32 publications

Interactions mechanism of commonly used drugs for the treatment of Covid-19

Interactions mechanism of commonly used drugs for the treatment of Covid-19

Fragment‐based discovery of flexible inhibitor targeting wild‐type acetohydroxyacid synthase and P197L mutant

Future direction of agrochemical development for plant disease in China

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