Abstract：
:Structural genomics will yield an immense number of protein three-dimensional structures in the near future. Automated theoretical methodologies are needed to exploit this information and are likely to play a pivotal role in drug discovery. Here, we present a fully automated, efficient docking methodology that does not require any a priori knowledge about the location of the binding site or function of the protein. The method relies on a multiscale concept where we deal with a hierarchy of models generated for the potential ligand. The models are created using the k-means clustering algorithm. The method was tested on seven protein-ligand complexes. In the largest complex, human immunodeficiency virus reverse transcriptase/nevirapin, the root mean square deviation value when comparing our results to the crystal structure was 0.29 A. We demonstrate on an additional 25 protein-ligand complexes that the methodology may be applicable to high throughput docking. This work reveals three striking results. First, a ligand can be docked using a very small number of feature points. Second, when using a multiscale concept, the number of conformers that require to be generated can be significantly reduced. Third, fully flexible ligands can be treated as a small set of rigid k-means clusters.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Glick M,Grant GH,Richards WGdoi
10.1021/jm020830ikeywords:
subject
Has Abstractpub_date
2002-10-10 00:00:00pages
4639-46issue
21eissn
0022-2623issn
1520-4804pii
jm020830ijournal_volume
45pub_type
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更新日期：2006-08-10 00:00:00
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pub_type： 杂志文章
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更新日期：2007-08-09 00:00:00
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doi：10.1021/acs.jmedchem.5b01369
更新日期：2016-01-28 00:00:00
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更新日期：2013-09-26 00:00:00
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更新日期：2013-12-12 00:00:00
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journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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更新日期：2017-07-27 00:00:00
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journal_title：Journal of medicinal chemistry
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abstract：:A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactiva...
journal_title：Journal of medicinal chemistry
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更新日期：2010-12-09 00:00:00
