Comparison of docking methods for carbohydrate binding in calcium-dependent lectins and prediction of the carbohydrate binding mode to sea cucumber lectin CEL-III

Lectins display a variety of strategies for specific recognition of carbohydrates. In several lectin families from different origin, one or two calcium ions are involved in the carbohydrate binding site with direct coordination of the sugar hydroxyl groups. Our work implied a molecular docking study involving a set of bacterial and animal calcium-dependant lectins in order to compare the ability of three docking programs to reproduce key carbohydrate-metal interactions. Flexible docking was performed using AutoDock, DOCK and Grid-based Ligand Docking with Energetics ( GLIDE) softwares. All docking packages were almost able to predict the carbohydrate binding orientations but not in every instance the result was obvious to evaluate. DOCK showed good results according to crystallographic information but not in all tested cases the lowest energy conformation identified the experimental data. GLIDE presented the same difficulty in result analysis but the lowest energy pose was always a satisfactory solution, able to mimic the real carbohydrate orientation. AutoDock showed a reasonable accuracy in sugar orientation prediction based on docking cluster number ranking and most accurate distances between calcium and sugar hydroxyl groups. The latest program and GLIDE were used to predict the Gal and GalNAc binding mode in sea cucumber CEL-III, a new calcium-dependent lectin, that displays haemolytic and cytotoxic properties.