BACKGROUND: Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of the available software. METHODS: The two widely used pharmacophore modeling and screening software programs Discovery Studio and LigandScout were used to generate, validate, and prospectively apply COX-1 and -2 models. Selected virtual hits were tested in cell-free enzymatic assays. The correct retrieval of active compounds was compared. RESULTS: In the enzymatic testing, 10.5% of the tested hits for COX-2 and 6.6% of the predicted compounds for COX-1 were active. To directly compare the two models, both based on the same PDB entry, were selected for virtual screening. The two programs yielded vastly different hit lists, but both predicted active compounds. CONCLUSION: To obtain a comprehensive selection of active compounds, more than one program should be used for modeling.
BACKGROUND: Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of the available software. METHODS: The two widely used pharmacophore modeling and screening software programs Discovery Studio and LigandScout were used to generate, validate, and prospectively apply COX-1 and -2 models. Selected virtual hits were tested in cell-free enzymatic assays. The correct retrieval of active compounds was compared. RESULTS: In the enzymatic testing, 10.5% of the tested hits for COX-2 and 6.6% of the predicted compounds for COX-1 were active. To directly compare the two models, both based on the same PDB entry, were selected for virtual screening. The two programs yielded vastly different hit lists, but both predicted active compounds. CONCLUSION: To obtain a comprehensive selection of active compounds, more than one program should be used for modeling.
Authors: Md Bashir Uddin; Mohammad Nurul Alam; Mahmudul Hasan; S M Bayejed Hossain; Mita Debnath; Ruhena Begum; Mohammed A Samad; Syeda Farjana Hoque; Md Shahidur Rahman Chowdhury; Md Mahfujur Rahman; Md Mukter Hossain; Mohammad Mahmudul Hassan; Åke Lundkvist; Josef D Järhult; Mohamed E El Zowalaty; Syed Sayeem Uddin Ahmed Journal: Antibiotics (Basel) Date: 2022-01-13