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Pharmacophore Modelling and Screening: Concepts, Recent Developments and Applications in Rational Drug Design

  • Chinmayee Choudhury
  • G. Narahari SastryEmail author
Chapter
Part of the Challenges and Advances in Computational Chemistry and Physics book series (COCH, volume 27)

Abstract

Computational design of molecules with desired properties has become indispensable in many areas of research, particularly in the pharmaceutical industry and academia. Pharmacophore is one of the essential state-of-the-art techniques widely used in various ways in the computer-aided drug design projects. The pharmacophore modelling approaches have been an important part of many drug discovery strategies due to its simple yet diverse usage. It has been extensively applied for virtual screening, lead optimization, target identification, toxicity prediction and de novo lead design and has a huge scope for application in fragment-based drug design and lead design targeting protein–protein interaction interfaces and target-based classification of chemical space. In this chapter, we have briefly discussed the basic concepts and methods of generation of pharmacophore models. The diverse applications of the pharmacophore approaches have been discussed using number of case studies. We conclude with the limitations of the approaches and its wide scope for the future application depending on the research problem and the type of initial data available.

Keywords

Computer-aided drug design Pharmacophore mapping Receptor-based pharmacophore Ligand-based pharmacophore Pharmacophore features Pharmacophore fingerprints Virtual screening Pharmacophore searching Docking QSAR De novo design 

Abbreviations

ADMET

Absorption, distribution, metabolism, excretion, toxicity

CADD

Computer-aided drug design

CmaA1

Mycobacterial cyclopropane synthase

HHCPF

Hexadecahydro-1H-Cyclopenta[a]Phenanthrene Framework

HTS

High-throughput screening

MD

Molecular dynamics

Mtb

Mycobacterium tuberculosis

QSAR

Quantitative structure-activity relationship

TB

Tuberculosis

Notes

Acknowledgements

CC and GNS thank the Department of Science and Technology (DST), Government of India, for financial support in the forms of DST-INSPIRE Faculty Award [DST/INSPIRE/04/2016/000732] and JC Bose Fellowship, respectively.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Molecular ModellingIndian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Department of BiochemistryAll India Institute of Medical SciencesBasni, JodhpurIndia

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