A desirability function-based scoring scheme for selecting fragment-like class A aminergic GPCR ligands

A physicochemical property-based desirability scoring scheme for fragment-based drug discovery was developed for class A aminergic GPCR targeted fragment libraries. Physicochemical property distributions of known aminergic GPCR-active fragments from the ChEMBL database were examined and used for a d...

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Bibliographic Details
Published in:Journal of computer-aided molecular design 2015-01, Vol.29 (1), p.59-66
Main Authors: Kelemen, Ádám A., Ferenczy, György G., Keserű, György M.
Format: Article
Language:English
Subjects:
Animal Anatomy
Chemistry
Chemistry and Materials Science
Computer aided design
Computer Applications in Chemistry
Databases, Factual
Drug Discovery
Fragmentation
Histology
Libraries
Ligands
Molecular biology
Morphology
Nitrogen - chemistry
Oxygen - chemistry
Peptide Fragments - chemistry
Physical Chemistry
Physicochemical properties
Preprocessing
Proteins
Receptors, G-Protein-Coupled - chemistry
Receptors, G-Protein-Coupled - metabolism
Reproducibility of Results
Scoring
Screening
Signal transduction
Small Molecule Libraries
Structure-Activity Relationship
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Summary:A physicochemical property-based desirability scoring scheme for fragment-based drug discovery was developed for class A aminergic GPCR targeted fragment libraries. Physicochemical property distributions of known aminergic GPCR-active fragments from the ChEMBL database were examined and used for a desirability function-based score. Property-distributions such as log D (at pH 7.4), PSA, pK a (strongest basic center), number of nitrogen atoms, number of oxygen atoms, and the number of rotatable bonds were combined into a desirability score (FrAGS). The validation of the scoring scheme was carried out using both public and proprietary experimental screening data. The scoring scheme is suitable for the design of aminergic GPCR targeted fragment libraries and might be useful for preprocessing fragments before structure based virtual or wet screening.
ISSN:0920-654X
1573-4951
DOI:10.1007/s10822-014-9804-5