title: Hierarchical virtual screening approaches in small molecule drug discovery.
abstract: Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery.
authors: Structural Bioinformatics Team, Center for Life Science Technologies, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors: Ashutosh
authors: A
authors: Kumar
authors: Structural Bioinformatics Team, Center for Life Science Technologies, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan. Electronic address: kamzhang@riken.jp.
authors: Kam Y J
authors: KY
authors: Zhang
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D062105:Molecular Docking Simulation; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries
keywords: Hierarchical virtual screening; Molecular docking; Pharmacophore modeling; Similarity search