title: Large-scale reverse docking profiles and their applications.
abstract: BACKGROUND
  Reverse docking approaches have been explored in previous studies on drug discovery to overcome some problems in traditional virtual screening. However, current reverse docking approaches are problematic in that the target spaces of those studies were rather small, and their applications were limited to identifying new drug targets. In this study, we expanded the scope of target space to a set of all protein structures currently available and developed several new applications of reverse docking method.
  
  
  RESULTS
  We generated 2D Matrix of docking scores among all the possible protein structures in yeast and human and 35 famous drugs. By clustering the docking profile data and then comparing them with fingerprint-based clustering of drugs, we first showed that our data contained accurate information on their chemical properties. Next, we showed that our method could be used to predict the druggability of target proteins. We also showed that a combination of sequence similarity and docking profile similarity could predict the enzyme EC numbers more accurately than sequence similarity alone. In two case studies, 5-fluorouracil and cycloheximide, we showed that our method can successfully find identifying target proteins.
  
  
  CONCLUSIONS
  By using a large number of protein structures, we improved the sensitivity of reverse docking and showed that using as many protein structure as possible was important in finding real binding targets.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Lee
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
mesh_terms: D003513:Cycloheximide / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D003513:Cycloheximide; D005472:Fluorouracil