Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.
Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.
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DOI：
10.1021/acs.jmedchem.2c01681
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发表时间：
2023-05-11
影响因子：
7.3
通讯作者：
Arnold, Eddy
中科院分区：
文献类型：
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作者：
Chopra, Ashima;Bauman, Joseph D.;Ruiz, Francesc X.;Arnold, Eddy
X-ray crystallographic fragment screening (XCFS) uses fragment-sized molecules (∼60 to 300 Da) to access binding sites on proteins that may be inaccessible to larger drug-like molecules (>300 Da). Previous studies have shown that fragments containing halogen atoms bind more often to proteins than non-halogenated fragments. Here, we designed the Halo Library containing 46 halogenated fragments (including the “universal fragment” 4-bromopyrazole), a majority of which have been reported to bind to or inhibit one or more targets. The library was screened against the crystals of HIV-1 reverse transcriptase with the drug rilpivirine, yielding an overall hit rate of 26%. Two new binding sites were discovered, and several hot spots were identified. This small library may thus provide a convenient tool for rapidly assessing the feasibility of a target for XCFS, mapping hot spots and cryptic sites, as well as finding fragment binders that can be useful for developing drug leads.
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影响因子：
7.3
作者：
Bauman, Joseph D.;Patel, Disha;Dharia, Chhaya;Fromer, Marc W.;Ahmed, Sameer;Frenkel, Yulia;Vijayan, R. S. K.;Eck, J. Thomas;Ho, William C.;Das, Kalyan;Shatkin, Aaron J.;Arnold, Eddy
通讯作者：
Arnold, Eddy
影响因子：
4
作者：
Bauman, Joseph D.;Patel, Disha;Baker, Steven F.;Vijayan, R. S. K.;Xiang, Amy;Parhi, Ajit K.;Martinez-Sobrido, Luis;LaVoie, Edmond J.;Das, Kalyan;Arnold, Eddy
通讯作者：
Arnold, Eddy
影响因子：
3.9
作者：
Bauman JD;Harrison JJ;Arnold E
通讯作者：
Arnold E
影响因子：
2.2
作者：
Clark, Timothy;Hennemann, Matthias;Politzer, Peter
通讯作者：
Politzer, Peter
DOI：
10.1016/j.ddtec.2010.11.003
发表时间：
2010-01-01
期刊：
Drug discovery today. Technologies
影响因子：
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作者：
通讯作者：
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