Lectin–sugar interaction

Abstract

Although a steadily increasing number of protein–ligand docking experiments have been performed successfully, there are only few studies concerning protein–sugar interactions. In this study, we investigate the interaction of wheat germ agglutinin (WGA) with N‐acetylglucosamine and a number of its derivatives and predict the binding free energies using flexible docking techniques. To assess the quality of our predictions, we also determined those binding free energies experimentally in cell‐binding studies. The predicted binding site, ligand orientation, and details of the binding mode are in perfect agreement with the known crystal structure of WGA with a sialoglycopeptide. Furthermore, we obtained an excellent linear correlation of our predicted binding free energies with both our own data and experimental data from the literature [Monsigny, M., Roche, A.C., Sene, C., Maget Dana, R. & Delmotte, F. (1980) Eur. J. Biochem.104, 147–153.]. In both cases, predicted energies were within 1.0 kJ·mol−1 of the experimental value. These results illustrate the usefulness of docking‐based methods for the qualitative and quantitative prediction of protein–carbohydrate interactions. The insights gained from such theoretical studies may be used to complement the results from the still scarce crystal structures.

Advances in chemical probing of protein O-GlcNAc glycosylation: structural role and molecular mechanisms

“…In early years, the WGA interaction with O-GlcNAc and a number of derivatives was explored by diverse experimental techniques, [236][237][238][239] providing initial biophysical data and binding information. Subsequent computational studies by flexible molecular docking methods predicted the corresponding binding mode and free energies, 240 reproducing well the experimental data. This good correlation is arguably based on entropy-enthalpy compensation as reported previously by Jiménez-Barbero and coworkers, who employed NMR titration and bidimensional experiments combined with computational calculations to characterise the binding and three-dimensional solution structure of the complex between the WGA-B domain and N,N 0 ,N 00 -triacetylchitobiose [(GlcNAc) 3 ].…”

Binding Mechanisms in Supramolecular Complexes

“…[154] A comprehensive analysis of a great many complexes with biopolymers gave, for the "best" ligands, a rough correlation with the increasing number of non-hydrogen atoms, thereby leading to an affinity of about 6 kJ mol À1 per heavy atom with ligands that were not too large. [156] Phenomenological procedures can also be based on parameters that have no direct connection with physically defined interactions. Suitably scaled values Reviews 3932 www.angewandte.org for polar and nonpolar hydrogen bonds were used together with Lennard-Jones as well as desolvation potentials and new docking routines.…”

“…Suitably scaled values for polar and nonpolar hydrogen bonds were used together with Lennard-Jones as well as desolvation potentials and new docking routines. [156] Phenomenological procedures can also be based on parameters that have no direct connection with physically defined interactions. [157] Here again, calculated and experimental affinities correlate well in data comparisons for which the calibration is based on the utilized parameters themselves.…”

Bindungsmechanismen in supramolekularen Komplexen

“…[155] Mit passend skalierten Werten für polare und unpolare Wasserstoffbrü-cken, Lennard-Jones-sowie Desolvatisierungs-Potentialen und mit neuen Docking-Routinen konnten auch ohne explizite Entropiefaktoren die DG-Werte für die Wechselwirkung in Lectin-Zucker-Komplexen innerhalb eines Trainingsdatensatzes auf meist AE 1 kJ mol À1 genau reproduziert werden. [156] Phänomenologische Verfahren können auch auf Parametern basieren, die keinen unmittelbaren Bezug zu physikalisch definierten Wechselwirkungen aufweisen. [157] Auch hier korrelieren berechnete und experimentelle Affinitäten besonders linear beim Vergleich von Daten, die der Kalibrierung der verwendeten Parameter selber zugrunde liegen.…”