Development of a Web-Server for Identification of Common Lead Molecules for Multiple Protein Targets
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/.
KeywordsMulti-target drug design Polypharmacology Scaffold-based optimization Screening and docking Structure based ligand design
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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