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Article ID: 767 - Last Modified:

Two similar molecules were docked using the same grid. Only their initial conformation were different. Why are the poses generated by Glide for these two molecules different?

Numerical simulations inevitably have some degree of sensitivity to initial conditions. Even a minimization can end up in a different local minimum with small changes in the initial conformation. In a complex algorithm like Glide docking, these differences can produce different results, though usually these variations are more pronounced for poor binders. Glide does not sample bond lengths and bond angles - it only samples the torsional angles. So if the conformations involve differences in these parameters, different poses can be generated. Using different conformers is in fact a good way of increasing sampling to locate the best pose: this is an option for XP docking in the Virtual Screening Workflow.

If you are concerned about the consistency of results, you could consider using the Virtual Screening Workflow (VSW), and choose the ligand preparation option "Regularize input geometries". The regularization is accomplished by converting each input structure to a unique SMILES string and then back to 3D; this ensures that input structures that differ only in atom ordering, conformation, or geometry produce consistent results.

Keywords: similar molecules, different poses, results, VSW, Regularize input geometries

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