title: Importance of ligand conformational energies in carbohydrate docking: Sorting the wheat from the chaff.
abstract: Docking algorithms that aim to be applicable to a broad range of ligands suffer reduced accuracy because they are unable to incorporate ligand-specific conformational energies. Here, we develop a set of Carbohydrate Intrinsic (CHI) energy functions that quantify the conformational properties of oligosaccharides, based on the values of their glycosidic torsion angles. The relative energies predicted by the CHI energy functions mirror the conformational distributions of glycosidic linkages determined from a survey of oligosaccharide-protein complexes in the protein data bank. Addition of CHI energies to the standard docking scores in Autodock 3, 4.2, and Vina consistently improves pose ranking of oligosaccharides docked to a set of anticarbohydrate antibodies. The CHI energy functions are also independent of docking algorithm, and with minor modifications, may be incorporated into both theoretical modeling methods, and experimental NMR or X-ray structure refinement programs.
authors.affiliation: Complex Carbohydrate Research Center, 315 Riverbend Road, University of Georgia, Athens, Georgia, 30606.
authors.forename: Anita K
authors.initials: AK
authors.lastname: Nivedha
authors.forename: Spandana
authors.initials: S
authors.lastname: Makeneni
authors.forename: Bethany Lachele
authors.initials: BL
authors.lastname: Foley
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Tessier
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D013816:Thermodynamics
chemical_list: D000906:Antibodies; D002241:Carbohydrates; D008024:Ligands
keywords: antibody; autodock vina; carbohydrate; docking; energy function