title: Anchor-GRIND: filling the gap between standard 3D QSAR and the GRid-INdependent descriptors.
abstract: The aim of this work is to present the anchor-GRIND methodology. Anchor-GRIND efficiently combines a priori chemical and biological knowledge about the studied compounds with alignment-independent molecular descriptors derived from molecular interaction fields. Such descriptors are particularly useful for series of ligands sharing a common scaffold but with very diverse substituents. The method uses a specific position of the molecular structure (the "anchor point") to compare the spatial distribution of the molecular interaction fields of the substituents. The descriptors produced are more detailed and specific than the original GRIND while still avoiding the bias introduced by the alignment. Three data sets have been studied to demonstrate the usefulness of the anchor-GRIND methodology for 3D-QSAR modeling. The two first data sets respectively include congeneric series of the hepatitis C virus NS3 protease and of the acetylcholinesterase inhibitors. The third data set discriminates between factor Xa inhibitors of high and low affinity. In all the series presented, the models obtained with the anchor-GRIND are statistically sound and easy to interpret.
authors.affiliation: Research Unit on Biomedical Informatics (GRIB), IMIM/Universitat Pompeu Fabra, C/Dr. Aiguader, 80, E-08003 Barcelona, Spain.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fontaine
authors.forename: Manuel
authors.initials: M
authors.lastname: Pastor
authors.forename: Ismael
authors.initials: I
authors.lastname: Zamora
authors.forename: Ferran
authors.initials: F
authors.lastname: Sanz
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D015195:Drug Design; D065427:Factor Xa Inhibitors; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D015842:Serine Proteinase Inhibitors / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000110:Acetylcholinesterase; D002800:Cholinesterase Inhibitors; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases