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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Discovery of penicillin binding proteins (PBPs) inhibitors by blending Virtual Screening, Molecular Docking and Simulation studies

An integrated protocol of virtual screening involving molecular docking, pharmacophore probing, and simulations was established to identify small novel molecules targeting crucial residues involved in the penicillin binding proteins (PBPs) involved in bacterial cell wall biosynthesis. An excellent approach was made utilizing ligand and structure-based pharmacophore to identify common features and structure-based docking with respect to PBPs in leading to the development of novel inhibitors possessing new scaffolds. To our delight, multiple-substituted triazine derivatives series bearing a novel scaffold, of which structure is remarkably different from the existing β-lactam inhibitors, were designed. A structure-based pharmacophore mapping was developed to explore the binding sites of PBPs which were taken into consideration. Subsequently, virtual screening, ADMET searches were at work to narrow down the proposed hits to be forwarded as a potential drug likes candidates. Further, the binding patterns of the best-proposed hits were explored to understand the deeper insight for its structural optimization by employing it on molecular dynamic simulations of 500ps. Selectivity profile for the most promising candidates was studied, revealing significantly C series molecules C15 was found to be the most potent compounds among designed library. The proposed hits can be forwarded for further study against PBPs involved in bacterial peptidoglycan cell wall biosynthesis.

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References

    Desai, N., Makwana, A. and Rajpara, K. (2016). Synthesis and study of 1,3,5-triazine based thiazole derivatives as antimicrobial agents. Journal of Saudi Chemical Society, 20, pp.S334-S341.

    Gonzales, P., Pesesky, M., Bouley, R., Ballard, A., Biddy, B., Suckow, M., Wolter, W., Schroeder, V., Burnham, C., Mobashery, S., Chang, M. and Dantas, G. (2015). Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA. Nature Chemical Biology, 11(11), pp.855-861.

    Jana, S. and Singh, S. (2018). Identification of selective MMP-9 inhibitors through multiple e-pharmacophore, ligand-based pharmacophore, molecular docking, and density functional theory approaches. Journal of Biomolecular Structure and Dynamics, pp.1-22.

Mayurpankhi Buragohain1
Abha Vashishtha2
Surabhi Johari 2*

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Surabhi is currently an assistant professor at the School of Biosciences, Ghaziabad, UP, India, and will provide a 10 minute oral from the platform.

1Centre for Biotechnology and Bioinformatics
Dibrugarh University
Dibrugarh 786001, Assam India

2Institute of Management Sciences,
University Courses,
School of Biosciences,
Ghaziabad Uttar Pradesh
India 201002

Ph n: +91 120 2709865
surabhi.johari@imsuc.ac.in