title: Chemoinformatic analysis of combinatorial libraries, drugs, natural products, and molecular libraries small molecule repository.
abstract: A multiple criteria approach is presented, that is used to perform a comparative analysis of four recently developed combinatorial libraries to drugs, Molecular Libraries Small Molecule Repository (MLSMR) and natural products. The compound databases were assessed in terms of physicochemical properties, scaffolds, and fingerprints. The approach enables the analysis of property space coverage, degree of overlap between collections, scaffold and structural diversity, and overall structural novelty. The degree of overlap between combinatorial libraries and drugs was assessed using the R-NN curve methodology, which measures the density of chemical space around a query molecule embedded in the chemical space of a target collection. The combinatorial libraries studied in this work exhibit scaffolds that were not observed in the drug, MLSMR, and natural products databases. The fingerprint-based comparisons indicate that these combinatorial libraries are structurally different than current drugs. The R-NN curve methodology revealed that a proportion of molecules in the combinatorial libraries is located within the property space of the drugs. However, the R-NN analysis also showed that there are a significant number of molecules in several combinatorial libraries that are located in sparse regions of the drug space.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, Florida 34987, USA.
authors.forename: Narender
authors.initials: N
authors.lastname: Singh
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
authors.forename: Marc A
authors.initials: MA
authors.lastname: Giulianotti
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Richard A
authors.initials: RA
authors.lastname: Houghten
authors.forename: Jose L
authors.initials: JL
authors.lastname: Medina-Franco
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D006860:Hydrogen Bonding; D048088:Informatics; D008968:Molecular Conformation; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D012995:Solubility
chemical_list: D001688:Biological Products; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries