Molecular Modelling of Carbohydrate Ring Puckering

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Molecular Modelling of Carbohydrate Ring Puckering

Johann Hendrickx 1 , Vinh Tran 1 , Yves-Henri Sanejouand 1

1 UFIP, UMR CNRS 6286, Nantes, France

In order to study protein-carbohydrate interactions at the atomic scale, a standard approach consists in predicting in silico the binding of the carbohydrate to its protein receptor, using classical molecular docking methods.

The intrinsic flexibility of carbohydrates is generally taken into account, through free rotations existing mainly at the level of hydroxyl groups. However, in some cases such as glycosidases, glycosyltransferases, base excision repair enzymes, the puckering of the carbohydrate ring must also be taken into account. However, most molecular docking programs are not designed to modify the ring conformation of carbohydrates.

To overcome this lack of functionality, the ring can be pre-deformed before performing molecular docking tests. We use the Hill and Reilly method to describe and build the conformation of carbohydrate ring [⁠1]. This method offers the same descriptive power as previous methods such as Cremer-Pople one [2]⁠. However, it has the advantage of being able to construct the cartesian coordinates of the ring from the reduced parameters characterizing the puckering. The method uses the triangular decomposition of a ring into a reference plane and triangular flaps. The carbohydrate to be generated is patterned on the puckered cyclohexane model. No minimization is performed in order to preserve the initial ring conformations, so that carbohydrate relaxation can occur inside the protein receptor, once the complex is preformed.

Five and six-members carbohydrate ring can be described as covering 20 and 38 canonical states respectively. Only a part can exist in transition states that may occur in acid-catalyzed processes.

Proteocarb, a web application offering 3D carbohydrate models with an acceptable puckering for molecular docking tests has been implemented. The application has a regularly updated library of 193 monosaccharides. In addition, the user can upload his own monosaccharide structure. A first version of the application is available* on the UFIP lab website : ufip.univ-nantes.fr/tools/ .

* As of June 30th, 2019.

Hill, A. D.; Reilly, P. J. Puckering Coordinates of Monocyclic Rings by Triangular Decomposition. J. Chem. Inf. Model. 2007, 47 (3), 1031–1035.

Cremer, D. T.; Pople, J. A. A General Definition of Ring Puckering Coordinates. J. Am. Chem. Soc. 1975, 97 (6), 1354–1358.

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Leiden University / Leiden Institute of Chemistry lic.leidenuniv.nl

European Carbohydrate Organisation

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