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Importance of ligand conformational energies in carbohydrate docking: Sorting the wheat from the chaff
Author(s) -
Nivedha Anita K.,
Makeneni Spandana,
Foley Bethany Lachele,
Tessier Matthew B.,
Woods Robert J.
Publication year - 2013
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23517
Subject(s) - glycosidic bond , docking (animal) , chemistry , autodock , searching the conformational space for docking , conformational ensembles , computational chemistry , stereochemistry , protein structure , molecular dynamics , biochemistry , medicine , nursing , in silico , gene , enzyme
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.