title: Lead optimization using matched molecular pairs: inclusion of contextual information for enhanced prediction of HERG inhibition, solubility, and lipophilicity.
abstract: Previous studies of the analysis of molecular matched pairs (MMPs) have often assumed that the effect of a substructural transformation on a molecular property is independent of the context (i.e., the local structural environment in which that transformation occurs). Experiments with large sets of hERG, solubility, and lipophilicity data demonstrate that the inclusion of contextual information can enhance the predictive power of MMP analyses, with significant trends (both positive and negative) being identified that are not apparent when using conventional, context-independent approaches.
authors.affiliation: Information School, University of Sheffield, Sheffield S1 4DP, UK.
authors.forename: George
authors.initials: G
authors.lastname: Papadatos
authors.forename: Muhammad
authors.initials: M
authors.lastname: Alkarouri
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Gillet
authors.forename: Peter
authors.initials: P
authors.lastname: Willett
authors.forename: Visakan
authors.initials: V
authors.lastname: Kadirkamanathan
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Luscombe
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Bravi
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Richmond
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Pickett
authors.forename: Jameed
authors.initials: J
authors.lastname: Hussain
authors.forename: John M
authors.initials: JM
authors.lastname: Pritchard
authors.forename: Anthony W J
authors.initials: AW
authors.lastname: Cooper
authors.forename: Simon J F
authors.initials: SJ
authors.lastname: Macdonald
mesh_terms: D000465:Algorithms; D016208:Databases, Factual; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D015394:Molecular Structure; D012995:Solubility
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D008024:Ligands; D008055:Lipids