Identification of free fatty acid receptor 2 agonists using virtual screening.

Abstract:

:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BEDROC and RIE. The results revealed that electrostatic similarity search protocol using EON (ET combo) outperformed all other protocols with outstanding enrichment of >95% in top 1% and 2% of the dataset with an AUC of 0.958. Interestingly, the hit lists that are obtained from different virtual-screening methods are generally highly complementary to hits found from electrostatic similarity searching. These results suggest that considering electrostatic similarity searching first increases the chance of identifying more (and more diverse) active compounds from a virtual-screening campaign. Accordingly, prospective virtual screening using electrostatic similarity searching was used to identify novel FFAR2 ligands. The discovered compounds provide new chemical matter starting points for the initiation of a medicinal chemistry campaign.

journal_name

Bioorg Med Chem Lett

authors

Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

doi

10.1016/j.bmcl.2020.127460

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

127460

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30571-0

journal_volume

30

pub_type

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