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Pharmer: Efficient and Exact Pharmacophore Search

David Ryan Koes, Carlos J. Camacho
2011 Journal of Chemical Information and Modeling  
Two novel methods for organizing pharmacophore data, the Pharmer KDB-tree and Bloom fingerprints, enable Pharmer to perform an exact pharmacophore search of almost two million structures in less than a  ...  Pharmer is a new computational approach to pharmacophore search that scales with the breadth and complexity of the query, not the size of the compound library being screened.  ...  Acknowledgments This work was supported by grants 1R21GM087617-01A1 and R01GM097082-01 from the National Institute of Health. Lidio Meireles created the original pharmacophore SMARTs definitions.  ... 
doi:10.1021/ci200097m pmid:21604800 pmcid:PMC3124593 fatcat:fnc74e4gi5bxhpqwd7ezq7awue

Enabling Large-Scale Design, Synthesis and Validation of Small Molecule Protein-Protein Antagonists

David Koes, Kareem Khoury, Yijun Huang, Wei Wang, Michal Bista, Grzegorz M. Popowicz, Siglinde Wolf, Tad A. Holak, Alexander Dömling, Carlos J. Camacho, Bin Xue
2012 PLoS ONE  
Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with  ...  Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds  ...  The technology, referred to as AnchorQuery, performs an exact pharmacophore search of anchor-oriented virtual libraries of explicit conformations.  ... 
doi:10.1371/journal.pone.0032839 pmid:22427896 pmcid:PMC3299697 fatcat:inngxaidcnblvc5ezafseyqnuu

Drug Design by Pharmacophore and Virtual Screening Approach

Deborah Giordano, Carmen Biancaniello, Maria Antonia Argenio, Angelo Facchiano
2022 Pharmaceuticals  
Computational tools to create the pharmacophore model and to perform virtual screening are available and generated successful studies.  ...  Pharmacophore approaches represent one of the most interesting tools developed, by defining the molecular functional features needed for the binding of a molecule to a given receptor, and then directing  ...  searching.  ... 
doi:10.3390/ph15050646 pmid:35631472 pmcid:PMC9145410 fatcat:wzrl2d4yynhz3oq4gr5dzk3ek4

Repurposing Novobiocin for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyltransferase (Rv2421c) [article]

Ruben Cloete, Mohd Shahbaaz, Melanie Grobbelaar, Samantha L. Sampson, Alan Christoffels
2020 bioRxiv   pre-print
Molecular docking validation and molecular dynamics simulation analysis of the top five compounds indicated that the identified inhibitor molecules bind to Rv2421c with comparable efficiency as the substrate  ...  A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject to virtual ligand screening against the Prestwick Chemical Library and the ZINC database  ...  perform an exact pharmacophore match which accelerates the search algorithm [14] .  ... 
doi:10.1101/2020.07.30.228726 fatcat:s423uqza5zaw3i4gu6qxk2ndz4

Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint

Eduardo Solano-Gonzalez, Katherine M Coburn, Wenbo Yu, Gerald M Wilson, Elmar Nurmemmedov, Santosh Kesari, Elizabeth T Chang, Alexander D MacKerell, David J Weber, France Carrier
2021 Nucleic Acids Research  
Using the computational Site Identification by Ligand Competitive Saturation (SILCS) technology, structural biology and cell-based assays, we identify small molecules that directly and selectively bind  ...  As single agents, the probes specifically disrupt hnRNP A18-RNA interactions, downregulate Trx and CTLA-4 protein levels and inhibit proliferation of several cancer cell lines without affecting the viability  ...  ACKNOWLEDGEMENTS The authors would like to thank Madeline Wilson for her technical assistance with fluorescence anisotropy experiments and the University of Maryland Marlene and Stewart Greenebaum Comprehensive  ... 
doi:10.1093/nar/gkaa1254 pmid:33398344 pmcid:PMC7897483 fatcat:2spd2owtdnbb3ccsgrdl3tp754

Computational evaluation of natural compounds as potential inhibitors of human PEPCK-M: an alternative for lung cancer therapy

Baptista LPR, Sinatti VVC, Da Silva JHM, Dardenne LE, Guimarães AC
2019 Advances and Applications in Bioinformatics and Chemistry  
Subsequently, the set of natural compounds of the ZINC database was screened against HsPEPCK-M models using structure-based pharmacophore modeling and molecular docking approaches.  ...  The selected compounds were evaluated according to its chemical diversity and clustered based on chemical similarity.Results: The pharmacophore hypotheses, generated based on known PEPCK inhibitors, were  ...  Pharmer: efficient and exact pharmacophore search. J Chem Inf Model . 2011;51(6):1307–1314. doi:10.1021/ci200097m 33. Irwin JJ, Shoichet BK.  ... 
doaj:4a14ef6d04cb452ebe249082ca5e3a18 fatcat:3aiwa4l4fff4vpepnmuopfjtiq

Molecular Substructure Mining Approaches for Computer-Aided Drug Discovery A Review

C.N. Nicolaou, C.S. Pattichis
2006 Zenodo  
Its aim is to discover and characterize interesting 2D substructures present in chemical datasets.  ...  expert medicinal chemists who tend to view, organize and treat chemical compounds as a collection of their substructural parts.  ...  Two types of frameworks were proposed: Frameworks with exact atoms (B) and purely graph-based frameworks (C). Figure 3 . 3 : Methotrexate and its corresponding feature tree.  ... 
doi:10.5281/zenodo.2567369 fatcat:4vqfcjvfafauxkfei6bslez6vu

In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c)

Ruben Cloete, Mohd Shahbaaz, Melanie Grobbelaar, Samantha L. Sampson, Alan Christoffels, Jie Zheng
2021 PLoS ONE  
A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject tovirtual ligand screening against the Prestwick Chemical Library and the ZINC database  ...  Novobiocin salt interacts with a MG ion and active site residues His20, Thr86, Gly107 and Leu164 similar to substrate DND of Mycobacterium tuberculosis Rv2421c.  ...  perform an exact pharmacophore match which accelerates the search algorithm [13] .  ... 
doi:10.1371/journal.pone.0259348 pmid:34727137 pmcid:PMC8562812 fatcat:artf2i2eofhbdknym4xxwpdrem

Next generation 3D pharmacophore modeling

Dora Šribar, Theresa Noonan, Lihua Deng, Trung Ngoc Nguyen, Szymon Pach, David Machalz, Marcel Bermudez, Gerhard Wolber, David Schaller, Universitätsbibliothek Der FU Berlin, Universitätsbibliothek Der FU Berlin
2020
Other trends include the efficient usage of 3D pharmacophore information in machine learning and artificial intelligence applications or freely accessible web servers for 3D pharmacophore modeling.  ...  In this review, we provide an overview on the basic concept of this method and summarize key studies for applying 3D pharmacophore models in virtual screening and mechanistic studies for protein functionality  ...  Although the exact definition and implementation of pharmacophore features and their characteristics may differ between different 3D pharmacophore modeling programs, the underlying concept of 3D pharmacophores  ... 
doi:10.17169/refubium-27008 fatcat:jrn2lcfyvbhdvnm266iqqt72zu