Identification of estrogen receptor α ligands with virtual screening techniques
Niinivehmas, S., Manivannan, E., Rauhamäki, S., Huuskonen, J., & Pentikäinen, O. (2016). Identification of estrogen receptor α ligands with virtual screening techniques. Journal of Molecular Graphics and Modelling, 64(March), 30-39. https://doi.org/10.1016/j.jmgm.2015.12.006
Published inJournal of Molecular Graphics and Modelling
DisciplineSolu- ja molekyylibiologiaOrgaaninen kemiaNanoscience CenterCell and Molecular BiologyOrganic ChemistryNanoscience Center
© 2015 Elsevier Inc. This is a preprint version of an article whose final and definitive form has been published by Elsevier.
Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example, structure-based methods identified an already known active ligand from the widely-used bechmarking decoy molecule set. Although prospective VS against one commercially available database with around 100,000 drug-like molecules did not retrieve many testworthy hits, one novel hit molecule with pIC50 value of 6.6, was identified. Furthermore, our small in-house compound collection of easy-to-synthesize molecules was virtually screened against ERα, yielding to five hit candidates, which were found to be active in vitro having pIC50 values from 5.5 to 6.5. ...
PublisherElsevier Inc.; Molecular Graphics and Modelling Society
Publication in research information system
MetadataShow full item record
Showing items with similar title or keywords.
Ahinko, Mira; Kurkinen, Sami; Niinivehmas, Sanna; Pentikäinen, Olli; Postila, Pekka (MDPI Center, 2019)Negative image-based (NIB) screening is a rigid molecular docking methodology that can also be employed in docking rescoring. During the NIB screening, a negative image is generated based on the target protein’s ...
Jokinen, Elmeri M.; Postila, Pekka A.; Ahinko, Mira; Niinivehmas, Sanna; Pentikäinen, Olli T. (Wiley-Blackwell Publishing, Inc., 2019)A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific ...
Virtanen, Salla (University of Jyväskylä, 2013)
Niinivehmas, Sanna (University of Jyväskylä, 2015)
Identification of a ligand on the Wip1 bacteriophage highly specific for a receptor on B. anthracis. Kan, Sherry; Fornelos Martins, Nadine; Schuch, Raymond; Fischetti, Vincent (American Society for Microbiology, 2013)Tectiviridae is a family of tailless bacteriophages with Gram-negative and Gram-positive hosts. The family model PRD1 and its close relatives all infect a broad range of enterobacteria by recognizing a plasmid-encoded ...