Virtual screening for novel 1-deoxy-d-xylulose-5-phosphate reductoisomerase inhibitors: A shape-based search approach

Prasan Tangyuenyongwatana, Wandee Gritsanapan

Abstract


A virtual screening study with ArgusLab 4.0.1 was performed on 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme in the methyl erythritol phosphate pathway in isoprenoids production which is present in malarial parasite Plasmodium falciparum. This enzyme has been shown to be the molecular target for fosmidomycin, a promising antimalarial drug. However, fosmidomycin has poor pharmacokinetic properties and low intestinal absorption. In this study, a subset of ZINC12 database composed of 7,478 molecules was docked on DXR (PDB ID: 5JO0) with ArgusDock (shape-based search algorithm) in the ArgusLab program to find a hit that correlates with fosmidomycin analogues. The shape-based search algorithm was chosen for the virtual screening of a large database on a computer due to its fast docking capability. The output screening compounds from this study were ZINC68966127, ZINC17111644, and ZINC59231267. These three compounds possess the required ligand-enzyme interactions as shown in fosmidomycin analogue 6b. In conclusion, shape-based search algorithm in ArgusLab 4.0.1 is an alternative method for performing virtual screening study on 3D database to develop novel antimalarial drugs.

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References

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