pp 1-18 | Cite as

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

  • Abhilash Jayaraj
  • Ruchika Bhat
  • Amita Pathak
  • Manpreet Singh
  • B. Jayaram
Protocol
Part of the Methods in Pharmacology and Toxicology book series

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/.

Keywords

Multi-target drug design Polypharmacology Scaffold-based optimization Screening and docking Structure based ligand design 

Notes

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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Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  • Abhilash Jayaraj
    • 1
    • 2
  • Ruchika Bhat
    • 1
    • 2
  • Amita Pathak
    • 1
    • 2
  • Manpreet Singh
    • 2
  • B. Jayaram
    • 1
    • 2
    • 3
  1. 1.Department of ChemistryIndian Institute of Technology DelhiNew DelhiIndia
  2. 2.Supercomputing Facility for Bioinformatics & Computational BiologyIndian Institute of Technology DelhiNew DelhiIndia
  3. 3.Kusuma School of Biological SciencesIndian Institute of Technology DelhiNew DelhiIndia

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