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Identification of Novel Protein Targets of Prodigiosin for Breast Cancer Using Inverse Virtual Screening Methods

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Abstract

Prodigiosin (PG) is chemically formulated as 4-methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2ylidene)methyl]-2,2′-bi-1H-pyrrole and it is an apoptotic agent. Only a few protein targets for PG have been identified so far for regulating various diseases; nevertheless, finding more PG targets is crucial for novel drug discovery research. A bioinformatics method was applied in this work to find additional potential PG targets. Initially, a text mining analysis was conducted to determine the relationship between PG and a variety of metabolic processes. One hundred sixteen proteins from the KEGG pathway were selected for the docking study. Inverse virtual screening was performed by Discovery Studio software 4.1 using CHARMm-based docking tool. Twelve proteins are screened out of 116 because their CDOCKER interaction energy is larger than − 40.22 kcal/mol. The best docking score with PG was reported to be − 44.25 kcal/mol, − 44.99 kcal/mol, and − 40.91 kcal/mol for three novel proteins, such as human epidermal growth factor-2 (HER-2), mitogen-activated protein kinase (MEK), and S6 kinase protein (S6K) respectively. The interactions in the S6K/PG complex are predominantly hydrophobic; however, hydrogen bond interactions can be identified in the MEK/PG and HER-2/PG complexes. The root-mean-square deviation (RMSD) and key interaction score system (KISS) were further used to validate the docking approach. The docking approach employed in this work has a low RMSD value (2.44 Å) and a high KISS score (0.5), indicating that it is significant.

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Data Availability

The data generated or obtained during this research's experiment is available to the associated author (Tania Paul), and can be made available to this journal at a fair cost upon request.

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Acknowledgements

Miss. Tania Paul, Mr. Prashant Bhardwaj, Dr. Tarun Kanti Bandyopadhyay, and Dr. Biswanath Bhunia would like to express their heartfelt gratitude to the Director of NIT Agartala for his constant support and encouragement.

Funding

This material is based upon the work supported by the National Institute of Technology, Agartala, India. Dr. Bhunia would like to acknowledge DST, Govt. of India, for Fast Track Young Scientist financial support (SERC/LS-167/2012). Tania Paul would like to express their gratitude to the Department of Bio Engineering, NIT Agartala, for financial support.

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Authors and Affiliations

  1. Department of Chemical Engineering, National Institute of Technology, Agartala, 799046, India

    Tania Paul & Tarun Kanti Bandyopadhyay

  2. Department of Computer Science and Engineering, National Institute of Technology, Agartala, 799046, India

    Prashant Bhardwaj

  3. Department of Chemical Engineering, Birla Institute of Technology Mesra, Mesra, Jharkhand, 835215, India

    Abhijit Mondal

  4. Department of Biotechnology, National Institute of Technology, Durgapur, India

    Nibedita Mahata

  5. Department of Bio Engineering, National Institute of Technology, Agartala, 799046, India

    Biswanath Bhunia

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  1. Tania Paul
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by Tania Paul and Prashant Bhardwaj, and analysis was performed by Biswanath Bhunia and Tarun Kanti Bandyopadhyay. The first draft of the manuscript was written by Abhijit Mondal and Nibedita Mahata and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Biswanath Bhunia.

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Paul, T., Bhardwaj, P., Mondal, A. et al. Identification of Novel Protein Targets of Prodigiosin for Breast Cancer Using Inverse Virtual Screening Methods. Appl Biochem Biotechnol 195, 7236–7254 (2023). https://doi.org/10.1007/s12010-023-04426-9

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