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Development of a Web-Server for Identification of Common Lead Molecules for Multiple Protein Targets

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Multi-Target Drug Design Using Chem-Bioinformatic Approaches

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

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Abstract

Due to increasing unresponsiveness of drugs to single targets in the form of resistance or presence of alternate mechanisms in case of complex diseases and disorders, etc., the focus is shifting towards polypharmacology. It is desirable that a drug works on multiple targets to elicit guaranteed/multiplier effect. Here, we provide a one stop solution to the quest of finding common leads for multiple protein targets. The computational protocol designed involves screening, docking, and scaffold-based optimization of hit molecules from a variety of compound libraries against any two specified protein targets. The protocol is validated with five case studies involving five pairs of proteins with varying active site similarities. The methodology is able to recover the known common FDA approved drugs against them. A web-server named “Multi-Target Ligand Design” is created and made freely accessible at http://www.scfbio-iitd.res.in/multitarget/.

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Acknowledgment

Funding from the Department of Biotechnology, Govt. of India, to SCFBio is gratefully acknowledged. A.J. and A.P. are Institute Fellows. R.B. is a DST INSPIRE Fellow.

Author contributions: B.J. conceived the project. A.J., R.B., A.P. carried out the computational development. All authors analyzed the results and wrote the manuscript. M.S. helped in web enabling of the server. All authors have given approval to the final version of the manuscript.

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Author notes

  1. Abhilash Jayaraj and Ruchika Bhat contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India

    Abhilash Jayaraj, Ruchika Bhat, Amita Pathak & B. Jayaram

  2. Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology Delhi, New Delhi, India

    Abhilash Jayaraj, Ruchika Bhat, Amita Pathak, Manpreet Singh & B. Jayaram

  3. Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India

    B. Jayaram

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  1. Abhilash Jayaraj
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  2. Ruchika Bhat
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Correspondence to B. Jayaram .

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Editors and Affiliations

  1. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

    Kunal Roy

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Jayaraj, A., Bhat, R., Pathak, A., Singh, M., Jayaram, B. (2018). Development of a Web-Server for Identification of Common Lead Molecules for Multiple Protein Targets. In: Roy, K. (eds) Multi-Target Drug Design Using Chem-Bioinformatic Approaches. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2018_9

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  • DOI: https://doi.org/10.1007/7653_2018_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8732-0

  • Online ISBN: 978-1-4939-8733-7

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