Abstract
Objective: The recent growth of highly resoluted crystallographic structures, together with the continuous improvements of the computing power, has established molecular docking as a leading drug design technique. However, the problems concerning the receptor flexibility and the lowered ability of docking software to correctly score the occurred interactions in some receptors are still relevant. Methods: Recently, several research groups have reported an enhancement in enrichment values when ensemble docking has been applied. Therefore, we utilized the latest technique for a dataset of Monoamine Oxidase–B (MAO-B) inhibitors. The docking program GOLD 5.3 was used in our study. Several docking parameters (grid space, scoring functions and ligand flexibility) were altered in order to achieve the optimal docking protocol. Results: The results of 200 000+docking simulations are represented in a modest table. The ensembled simulations demonstrated low ability of the docking software to correctly score the actives seeded in the dataset. However, the superimposed complex-1S3B-1OJA-1OJC, achieved a moderate enrichment value equaled to 9. No significant improvements were noted when five complexed receptors were employed. Conclusion: As a conclusion, it should be noted that in some cases the ensemble docking enhanced the database enrichments, however overall the value is not suitable for future virtual screening. Further investigations in that area should be considered.
Highlights
Molecular docking is the most common structure-based technique utilized for the virtual design and development of novel molecules
We started our study with the pre-docking operations, which are described in the materials and methods section of this paper
We proceed with self-docking simulations in order to evaluate the ability of GOLD 5.3 to correctly position and score the removed cocrystallized ligands
Summary
Molecular docking is the most common structure-based technique utilized for the virtual design and development of novel molecules It observes the interactions between a ligand and a receptor applying searching and scoring algorithms [1]. The recent growth of highly resoluted crystallographic structures, together with the enhanced computer power, established molecular docking as a leading drug design technique [2]. Few downsides such as receptor flexibility [3] and the inability of the docking softwares to correctly score the occurring bonds [4] are still relevant. The inducement of ensembles cannot always enhance the enrichment values as reported by Rao et al [10]
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