title: LIGSIFT: an open-source tool for ligand structural alignment and virtual screening.
abstract: BACKGROUND
  Shape-based alignment of small molecules is a widely used approach in computer-aided drug discovery. Most shape-based ligand structure alignment applications, both commercial and freely available ones, use the Tanimoto coefficient or similar functions for evaluating molecular similarity. Major drawbacks of using such functions are the size dependence of the score and the fact that the statistical significance of the molecular match using such metrics is not reported.
  
  
  RESULTS
  We describe a new open-source ligand structure alignment and virtual screening (VS) algorithm, LIGSIFT, that uses Gaussian molecular shape overlay for fast small molecule alignment and a size-independent scoring function for efficient VS based on the statistical significance of the score. LIGSIFT was tested against the compounds for 40 protein targets available in the Directory of Useful Decoys and the performance was evaluated using the area under the ROC curve (AUC), the Enrichment Factor (EF) and Hit Rate (HR). LIGSIFT-based VS shows an average AUC of 0.79, average EF values of 20.8 and a HR of 59% in the top 1% of the screened library.
  
  
  METHODS
  LIGSIFT software, including the source code, is freely available to academic users at http://cssb.biology.gatech.edu/LIGSIFT.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
  
  
  BACKGROUND
  skolnick@gatech.edu.
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, GA 30076, USA.
authors.forename: Ambrish
authors.initials: A
authors.lastname: Roy
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, GA 30076, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D062126:Databases, Chemical; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D011506:Proteins