Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening.
Mol Inform
; 36(1-2)2017 01.
Article
in En
| MEDLINE
| ID: mdl-27650559
ABSTRACT
Molecular descriptors capture diverse structural information of molecules and are a prerequisite for ligand-based similarity searching. In this study, we introduce topological matrix-based descriptors to virtual screening for hit discovery. We evaluated the usefulness of matrix-based descriptors in a retrospective setting and compared them with topological pharmacophore descriptors. Special attention was given to the influence of data pre-processing and the applied similarity metric on the virtual screening performance. Overall, the MB descriptors showed a competitive and complementary performance to other descriptors. A prospective screen of a commercial compound library led to the discovery of a novel natural-product-derived cyclooxygenase-2 inhibitor predicted to interact differently with the target protein compared to the query compound ibuprofen. The results of our study motivate the use of matrix-based descriptors for molecular similarity-based virtual screening and scaffold hopping.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Quantitative Structure-Activity Relationship
/
Small Molecule Libraries
/
Molecular Docking Simulation
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Language:
En
Journal:
Mol Inform
Year:
2017
Document type:
Article
Affiliation country:
Italia