title: Performance evaluation of 2D fingerprint and 3D shape similarity methods in virtual screening.
abstract: Virtual screening (VS) can be accomplished in either ligand- or structure-based methods. In recent times, an increasing number of 2D fingerprint and 3D shape similarity methods have been used in ligand-based VS. To evaluate the performance of these ligand-based methods, retrospective VS was performed on a tailored directory of useful decoys (DUD). The VS performances of 14 2D fingerprints and four 3D shape similarity methods were compared. The results revealed that 2D fingerprints ECFP_2 and FCFP_4 yielded better performance than the 3D Phase Shape methods. These ligand-based methods were also compared with structure-based methods, such as Glide docking and Prime molecular mechanics generalized Born surface area rescoring, which demonstrated that both 2D fingerprint and 3D shape similarity methods could yield higher enrichment during early retrieval of active compounds. The results demonstrated the superiority of ligand-based methods over the docking-based screening in terms of both speed and hit enrichment. Therefore, considering ligand-based methods first in any VS workflow would be a wise option.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Hu
authors.forename: Guanglin
authors.initials: G
authors.lastname: Kuang
authors.forename: Wen
authors.initials: W
authors.lastname: Xiao
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: Guixia
authors.initials: G
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry
chemical_list: D008024:Ligands; C527701:enhanced cyan fluorescent protein; D049452:Green Fluorescent Proteins; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A