Evaluation of docking programs for predicting binding of Golgi α‐mannosidase II inhibitors: A comparison with crystallography

Abstract

Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a promising target for drug development in anti-tumor therapies. Using X-ray crystallography, we have determined the structure of Drosophila melanogaster GMII (dGMII) complexed with three different inhibitors exhibiting IC50's ranging from 80 to 1000 microM. These structures, along with those of seven other available dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We found that small inhibitors could be accurately docked by most of the software, while docking of larger compounds (i.e., those with extended aromatic cycles or long aliphatic chains) was more problematic. Overall, Glide provided the best docking results, with the most accurately predicted binding around the active site zinc atom. Further evaluation of Glide's performance revealed its ability to extract active compounds from a benchmark library of decoys.

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

“…The commercial package GLIDE slightly outperformed the other academic available docking engines in terms of RMSD from experimental structures but the best result did not always correspond to the lowest energy conformation. This conclusion is in agreement with recent evaluation study for docking carbohydrate derivative to Zn-containing enzyme [37]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 One calcium β-sandwich bacterial lectin…”

Docking Ligands into Flexible and Solvated Macromolecules. 6. Development and Application to the Docking of HDACs and other Zinc Metalloenzymes Inhibitors

“…8 In 2007, the first version of FITTED was tested for its ability to dock mannosidase inhibitors which revealed the intricacies of modeling zinc coordination. 4 Later on, we also demonstrated that scoring metalloenzyme inhibitors was poor. 9 Throughout the years, docking programs have been assessed for their ability to dock inhibitors coordinating metal ions (often zinc) of metalloenzymes: AutoDock, DOCK, GOLD, and FlexX being widely used.…”

N-(4-Substituted-benzoyl)-N′-(β-d-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods

“…Docking was carried out using the Glide v4.5 package of Schrodinger suite 2007. 37 Recent review of docking programs showed 47 that Glide belongs amongst the most accurate docking programs.…”