title: Virtual fragment screening: exploration of MM-PBSA re-scoring.
abstract: An NMR fragment screening dataset with known binders and decoys was used to evaluate the ability of docking and re-scoring methods to identify fragment binders. Re-scoring docked poses using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) implicit solvent model identifies additional active fragments relative to either docking or random fragment screening alone. Early enrichment, which is clearly most important in practice for selecting relatively small sets of compounds for experimental testing, is improved by MM-PBSA re-scoring. In addition, the value in MM-PBSA re-scoring of docked poses for virtual screening may be in lessening the effect of the variation in the protein complex structure used.
authors.affiliation: Infection Innovative Medicines Unit, Chemistry Department, AstraZeneca, R&D Boston, Waltham, MA 02451, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Kawatkar
authors.forename: Demetri
authors.initials: D
authors.lastname: Moustakas
authors.forename: Matthew
authors.initials: M
authors.lastname: Miller
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000737:chemistry*; D008024:Ligands; D054834:Lipocalins / Q000737:chemistry*; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D008024:Ligands; D054834:Lipocalins; D011506:Proteins; D054852:Small Molecule Libraries; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase