Importance of ligand conformational energies in carbohydrate docking: Sorting the wheat from the chaff

• Published in: Journal of computational chemistry Vol. 35; no. 7; pp. 526 - 539
• Main Authors: Nivedha, Anita K., Makeneni, Spandana, Foley, Bethany Lachele, Tessier, Matthew B., Woods, Robert J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 15.03.2014; Wiley Subscription Services, Inc
• Subjects: Algorithms; Antibodies; Antibodies - chemistry; Antibodies - metabolism; antibody; autodock vina; Bioenergetics; carbohydrate; Carbohydrate Metabolism; Carbohydrate Sequence; Carbohydrates; Carbohydrates - chemistry; Classification; Data banks; Docking; energy function; Ligands; Mathematical models; Molecular Conformation; Molecular Docking Simulation; Molecular Sequence Data; NMR; Nuclear magnetic resonance; Oligosaccharides; Proteins; Sorting algorithms; Thermodynamics; Wheat; docking; autodock vina; energy function; antibody; carbohydrate
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.23517

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. © 2013 Wiley Periodicals, Inc. A set of carbohydrate intrinsic (CHI) energy functions that quantify the conformational properties of oligosaccharides are introduced, based on the values of their glycosidic torsion angles. Augmenting the interaction energies predicted by automated docking (AutoDock 3, AutoDock 4.2, and AutoDock Vina) with CHI energies significantly increases the correlation between the docked energy and the structure correctness, for a test suite of carbohydrate–protein complexes.