Comparison of Automatic Three-Dimensional Model Builders Using 639 X-ray Structures

Sadowski, Jens; Gasteiger, Johann; Klebe, G.

doi:10.1021/ci00020a039

Cited by 614 publications

(500 citation statements)

References 2 publications

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“…The generator is graph-based and employs a SMILES (simplified molecular input line entry specification) [81] string representation of the molecules as well as SMARTS (SMILES arbitrary target specification) in its engine. It is built around Marvin Reactor [82], and the Corina code [83] provides force-field optimized 3-dimensional structures. A detailed description of the library generator is in preparation.…”

Section: A Molecular Candidate Librariesmentioning

confidence: 99%

The Harvard Clean Energy Project: Large-Scale Computational Screening and Design of Organic Photovoltaics on the World Community Grid

Hachmann

Olivares‐Amaya

Atahan-Evrenk

et al. 2011

J. Phys. Chem. Lett.

591

565

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This perspective article introduces the Harvard Clean Energy Project (CEP), a theory-driven search for the next generation of organic solar cell materials. We give a broad overview of its setup and infrastructure, present first results, and outline upcoming developments.CEP has established an automated, high-throughput, in silico framework to study potential candidate structures for organic photovoltaics. The current project phase is concerned with the characterization of millions of molecular motifs using first-principles quantum chemistry. The scale of this study requires a correspondingly large computational resource which is provided by distributed volunteer computing on IBM's World Community Grid. The results are compiled and analyzed in a reference database and will be made available for public use. In addition to finding specific candidates with certain properties, it is the goal of CEP to illuminate and understand the structure-property relations in the domain of organic electronics. Such insights can open the door to a rational and systematic design of future high-performance materials. The computational work in CEP is tightly embedded in a collaboration with experimentalists, who provide valuable input and feedback to the project.

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Section: A Molecular Candidate Librariesmentioning

confidence: 99%

The Harvard Clean Energy Project: Large-Scale Computational Screening and Design of Organic Photovoltaics on the World Community Grid

Hachmann

Olivares‐Amaya

Atahan-Evrenk

et al. 2011

J. Phys. Chem. Lett.

591

565

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“…Each species was maintained on Mueller-Hinton agar (MHA), which was also used to confirm the absence of contamination and the validity of the inocula. Before testing, each species was recovered by subculturing in Mueller-Hinton broth (MHB), aerobically, for 24 h, at 37 C. Working concentrations of approximately 10 5 -10 6 cfu/ mL, used for antibacterial activity assays, were prepared by proper dilution of culture in microbiological medium. Compounds were dissolved in DMSO (2%) to prepare stock solutions at a concentration of 40 mg/mL, sterilized by filtration through a 0.22-mm membrane filter (Sartorius AG -Göttingen, Germany) according to Tepe et al and further diluted in MHB to a working solutions.…”

Section: The Antibacterial Activity Testingmentioning

confidence: 99%

“…Initial 3D structures of compounds 1-9 were generated from SMILES notation in CORINA assuming R stereochemistry for all stereogenic centers, except for C2 of the phenethyl moiety of compound 6 36,37 . The S stereochemistry was ascribed to this stereogenic center, on the ground of experimental data 30 .…”

Section: Molecular Modelingmentioning

confidence: 99%

Antiproliferative and antibacterial activity of some glutarimide derivatives

Popović‐Djordjević¹,

Klaus

Žižak

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Antiproliferative and antibacterial activities of nine glutarimide derivatives (1-9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC 50 ¼ 9-27 mM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6-8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 Â 10 À3 mol/L). Distinction between more and less active/ inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

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“…Further, Lipinski's Rule of Five (Lipinski et al, 2001) and PreADMET (Lee et al, 2004) were utilized to evaluate drug likeness for the pool, and ultimately 24 709 compounds passed the assessment and they defined a distinct library of natural products with diverse structures and high drug-likeness, which will be used in subsequent high-throughput virtual screening for discovery of potential Rho binders. The 3D conformations of these compounds were converted from their 2D structures using the CORINA program (Molecular Networks GmbH, Erlangen, Germany) (Sadowski et al, 1994) and then minimized by the MMFF94 force field (Halgren, 1996).…”

Section: Natural Product Librarymentioning

confidence: 99%

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension

Yan

et al. 2015

Pharmaceutical Biology

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(2015) Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension, Pharmaceutical Biology, 53:8, 1201-1206, DOI: 10.3109/13880209.2014 ORIGINAL ARTICLEStepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension Hao Su, Ji Yan, Jian Xu, Xi-Zhen Fan, Xian-Lin Sun, and Kang-Yu Chen Department of Cardiology, Anhui Provincial Hospital, Hefei, China Abstract Context: Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. Objective: In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. Materials and methods: In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. Results: With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC 50 ¼ 0.22 and 0.95 mM, respectively. Discussion and conclusion: Structural examination suggested that complicated networks of nonbonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

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Comparison of Automatic Three-Dimensional Model Builders Using 639 X-ray Structures

Cited by 614 publications

References 2 publications

The Harvard Clean Energy Project: Large-Scale Computational Screening and Design of Organic Photovoltaics on the World Community Grid

The Harvard Clean Energy Project: Large-Scale Computational Screening and Design of Organic Photovoltaics on the World Community Grid

Antiproliferative and antibacterial activity of some glutarimide derivatives

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension

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