title: Use of shape similarities for the classification of P-glycoprotein substrates and nonsubstrates.
abstract: BACKGROUND
  The multidrug transporter P-glycoprotein (P-gp) ATP-binding cassette B1 (ABCB1) is one of the key proteins influencing bioavailability and uptake of drugs in the brain. In addition, it is one of the main factors contributing to multidrug resistance in tumor therapy. Due to its promiscuous substrate recognition, prediction of substrate properties for the multidrug transporter P-gp represents a challenging task.
  
  
  RESULTS
  Here, we present data on three classification methods of ABCB1 substrates and nonsubstrates based on 2D and 3D shape similarity calculations with special emphasis on the use of the similarity-based relationship approach. The results indicate that a reference set structurally similar to the data set performs superiorly to those selected on the basis of maximum diversity and suggests Random Forest as the most suitable classification method for this data set.
  
  
  CONCLUSIONS
  This study suggests 2D descriptors representing 3D features best suited to the classification of P-gp substrates and nonsubstrates.
authors.affiliation: University of Vienna, Department for Medicinal Chemistry, Pharmacoinformatics Research Group, Althanstrasse 14, 1090 Wien, Austria.
authors.forename: Rita
authors.initials: R
authors.lastname: Schwaha
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Ecker
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D006801:Humans; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations