Design of Novel Dual-Target Hits Against Malaria and Tuberculosis Using Computational Docking

  • Manoj Kumar
  • Anuj SharmaEmail author
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


Drugs which are purposefully designed to hit more than one target (multi-target drugs) promise a better safety profile and low resistance probability. Multi-target therapy also offers a cost-effective model for pharmaceutical R&D, making it quite an appealing strategy in the domain of neglected tropical diseases (NTDs) and other infections/coinfections of the global impact such as malaria, tuberculosis, and AIDS. We reviewed herein different approaches (knowledge base and screening base) for designing multi-target inhibitors with the special emphasis on the research work of the authors. Additionally, a step-by-step guide (protocol) and different computational resources are also discussed in detail to design multi-target hits for malaria and tuberculosis.


AIDS AutoDock Computational docking Druglikeness Infectious diseases Ligand efficiency Malaria Multi-target drugs Multi-target screening Neglected tropical diseases Tuberculosis 



Two dimensional


Three dimensional


Advanced Chemistry Development, Inc.


Absorption, distribution, metabolism, excretion, and toxicity


AutoDock Tool


Acquired immune deficiency syndrome


Austin model 1


Assisted model building with energy refinement


Antimicrobial resistance


Binding energy


Biological magnetic resonance data bank


The Cambridge Crystallographic Data Centre


Chemistry at Harvard Macromolecular Mechanics


Chemical database of bioactive molecules with drug-like properties




Dihydrofolate reductase


Disease-modifying agents


Designed multiple ligands


Discovery Studio Visualizer


Directory of useful decoys


Epidermal growth factor receptor


European Bioinformatics Institute


Food and Drug Administration, USA


Genetic algorithm


Human immunodeficiency virus

In silico (syn in computo)

Performed on computer


Ligand efficiency


Lamarckian genetic algorithm


Local search


Mitogen-activated protein kinase


Molecular dynamics


Multidrug resistance


Molecular Graphics Laboratory tools


Molecular mechanics 2


Molegro Molecular Viewer


Multi-target drugs


Molecular weight


Nonsteroidal anti-inflammatory drugs


Neglected tropical diseases


Genomics, proteomics, or metabolomics


Pan-assay interference compounds


Protein Data Bank


Parameterized model number 3


Quantitative structure activity relationship


Research and development


Research Collaboratory for Structural Bioinformatics


Root-mean-square deviation


Simulated annealing


Shape-Feature Similarity


Search tool for interacting chemicals


Search tool for the retrieval of interacting genes/proteins




Traditional Chinese medicines


Total drug resistance


Thymidylate synthase


Therapeutic target database


Wild type


Extreme drug resistance


Zinc Is Not Commercial (ZINC database)



The authors gratefully acknowledge Science and Engineering Research Board (SERB), Govt. of India (Grant No. SER-892-CMD), to financially assist this work.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryIndian Institute of Technology RoorkeeRoorkeeIndia
  2. 2.Department of Chemistry and Chemical BiologyMcMaster UniversityHamiltonCanada

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