Abstract
Monopolar Spindle 1 (MPS1) protein kinases are crucial in metaphase to anaphase cellular transition. It is a primary element of spindle assembly checkpoint (SAC). This SAC is responsible for guarding the proper chromosomal segregation while any chromosomal instability hinders its normal functioning. The chromosomal instability may lead to aneuploidy and tumorigenesis. And it occurs mainly due to overexpression of MPS1 in many cancer types. Their effect could be reduced via MPS1 inhibition. The methanol extract of Pleurotus ostreatus possesses some medicinal qualities and has proven anti-cancerous properties. There is a need for proper screening and identification of molecules that have these anticancer properties and shows affinity against MPS1 with inhibition properties. So for this study, 29 bioactive compounds (handpicked through literature mining) of P. ostreatus were selected to identify a suitable drug candidate. Their ADME/T properties were analyzed, to predict the drug-likeness of mushroom compounds, based on Lipinski’s rule of 5 (RO5). The screening of these bioactive compounds and subsequent molecular docking against MPS1 provided compounds with the best conformation-based binding affinity. The best 2 complexes, i.e., MPS1-ergosterol and MPS1-ganoderic acid, were subjected to the molecular dynamics simulation. Both the complexes were observed for their affinity, stability, and flexibility in protein–ligand complex systems. The MD simulation study reveals that ergosterol has an energetically favorable binding affinity with MPS1. Results show that the formation of a hydrogen bond between Glu603 residue and ergosterol has strengthened the affinity of ergosterol with MPS1. Hence, this study identified ergosterol as a potential and novel inhibitor for MPS1 that could be a plausible drug candidate through this work.
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The authors are grateful to the Centre of Bioinformatics and Centre of Biotechnology, University of Allahabad for providing the access to the resources that were required to carry out this research work.
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Mishra, D., Mishra, A., Katara, P. et al. In silico identification of potential inhibitors of MPS1 from edible mushroom (Pleurotus ostreatus) to prevent aneuploidy and tumorigenesis. J Proteins Proteom 13, 175–185 (2022). https://doi.org/10.1007/s42485-022-00091-4
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DOI: https://doi.org/10.1007/s42485-022-00091-4