Pharmacophore Modelling
and Screening: Concepts, Recent
Developments and Applications
in Rational Drug Design
Chinmayee Choudhury and G. Narahari Sastry
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 Á Pharmacophore mapping
Receptor-based pharmacophore Á Ligand-based pharmacophore
Pharmacophore features Á Pharmacophore fingerprints Á Virtual screening
Pharmacophore searching Á Docking Á QSAR Á De novo design
Abbreviations
ADMET Absorption, distribution, metabolism, excretion, toxicity
CADD
Computer-aided drug design
CmaA1 Mycobacterial cyclopropane synthase
C. Choudhury Á G. Narahari Sastry (&)
Center for Molecular Modelling, Indian Institute of Chemical Technology,
Hyderabad, India
e-mail: gnsastry@gmail.com
C. Choudhury
Department of Biochemistry, All India Institute of Medical Sciences,
Basni, Jodhpur, Rajasthan, India
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_2
25
and Screening: Concepts, Recent
Developments and Applications
in Rational Drug Design
Chinmayee Choudhury and G. Narahari Sastry
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 Á Pharmacophore mapping
Receptor-based pharmacophore Á Ligand-based pharmacophore
Pharmacophore features Á Pharmacophore fingerprints Á Virtual screening
Pharmacophore searching Á Docking Á QSAR Á De novo design
Abbreviations
ADMET Absorption, distribution, metabolism, excretion, toxicity
CADD
Computer-aided drug design
CmaA1 Mycobacterial cyclopropane synthase
C. Choudhury Á G. Narahari Sastry (&)
Center for Molecular Modelling, Indian Institute of Chemical Technology,
Hyderabad, India
e-mail: gnsastry@gmail.com
C. Choudhury
Department of Biochemistry, All India Institute of Medical Sciences,
Basni, Jodhpur, Rajasthan, India
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_2
25