Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Schematic representation of the virtual screening (VS) protocol used in this study to select novel potential h15-LOX-2 inhibitors from the ZINC-Curated database. (A) Representation of the sequence of selection filters applied to the ZINC-Curated database in each VS step. (B) Schematic representation of the steps to generate the shape-based model that was used as the first filter in the VS protocol: 1. Alignment of low energy conformation structures of two known h15-LOX-2 inhibitors ( LIT-04 and LIT-05 ), using LigandScout’s alignment algorithm, and 2. Shape-based model generation using ROCS. The molecular shape surface is represented in gray. The figure was prepared by using LigandScout and ROCS.

Article Snippet: Babel , v.2.2.3 (Open Babel Development Team) was used to generate molecular fingerprints; FILTER module of OMEGA − v. v.2.5.1.5/v.4.1.2.0 (Openeye Scientific Sofware Inc., Santa Fe, NM) was used to filter the compounds database for drug-like properties and to check the presence of PAINS substructures in the structures of the identified inhibitors; GOLD , v.5.2 ( CCDC , T he Cambridge Crystallographic Data Center, Cambridge, U.K.) was used for docking; GraphPad Prism v.9/v.10 (GraphPad Software, Boston, MA) was used for experimental data analysis; LigandScout , v.4.4.7 (Inte:Ligand GmbH, Maria Enzersdorf, Austria) was used for protein–ligand interaction recognition; MoKa , v.2.6 (Molecular Discovery Ltd.., Borehamwood, U.K.) was used to attribute protonation states based on in silico predictions of p K a values; OMEGA − v.2.5.1.5 (Openeye Scientific Sofware Inc.., Santa Fe, NM) was used for conformers generation; Open Babel , v.2.3.1 (Open Babel Development Team) was used to generate 3D structures of compounds; PyMOL v.2.5.0 (Schrödinger Inc.., New York, NY) was used for protein’s structures visualization; QUACPAC v.2.0.0.3 (Openeye Scientific Sofware Inc., Santa Fe, NM) was used to generate tautomers and to attribute protonation states; ROCS , v.3.3.0.3/v.3.4.3.0 (Openeye Scientific Sofware Inc.., Santa Fe, NM) was used to perform shape-based screening; SwissADME , (University of Lausanne, Lausanne, Switzerland) was used for physicochemical properties and drug-likeness predictions; SYBYL-X v.2.1.1 (Certara Inc.., PA) was used for protein’s structure preparation for docking procedures and for protein’s solvent-accessible area calculations.

Techniques: Sequencing, Selection