In order to study the modalities of protein-carbohydrate interaction at the atomic scale, one of the standard methods consists in predicting in silico the binding of carbohydrate to its protein receptor, using a classical molecular docking method.
The intrinsic flexibility of carbohydrates is generally taken into account in prediction calculations, 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, one strategy is to pre-deform the ring before performing molecular docking tests.
We use the Hill and Reilly method to describe and build the conformation of carbohydrate ring (Hill and Reilly, 2007). This method offers the same descriptive power as previous methods such as Cremer-Pople (Cremer and Pople, 1975).
However, this method 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 as model.
No minimization is performed in order to preserve the initial ring conformations. The goal is for carbohydrate relaxation to 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.
A web application offering 3D carbohydrate models with an acceptable puckering for molecular docking tests is implemented.
The application has a regularly updated library of 193 monosaccharides. In addition, the user can upload his own monosaccharide structure.
Cremer, D. T. and Pople, J. A. (1975) 'A General Definition of Ring Puckering Coordinates', Journal of the American Chemical Society, 97(6), pp. 1354–1358. doi: https://www.doi.org/10.1021/ja00839a011.
Hill, A. D. and Reilly, P. J. (2007) 'Puckering coordinates of monocyclic rings by triangular decomposition', Journal of chemical information and modeling, 47(3), pp. 1031–5. doi: https://www.doi.org/10.1021/ci600492e.
This application only works with a monosaccharide contained in a PDB file. A next version is planned for an oligosaccharide on which the user will be able to choose the osidic ring to be deformed.
A library of 193 monosaccharides is regularly updated