initiated development of a disease (tuberculosis) specific Web portal, integrating all
these techniques, which will be of tremendous help for researches working in the
field of Mtb drug discovery [32].
Pharmacophore modelling is one of the enormously useful sub-areas of CADD
with diverse structure and ligand-based applications [33, 34]. Like docking, one of
the basic applications of pharmacophore models is virtual screening, but at a much
faster speed as compared to docking [33]. This approach can also be implemented
complementarily with docking and QSAR studies [18, 20]. Many studies use
pharmacophore models for target/off-target identification as well [35, 36]. In this
chapter, we basically focus on the in silico representation of the concept and the
varieties of ways of application of pharmacophore models in drug discovery projects.
2 The Concept of Pharmacophore
The term ‘pharmacophore’ has gained immense popularity in the field of medicinal
chemistry paralleled with computer-aided structure-activity relationship studies. In
1909, Ehrlich gave an introductory definition of pharmacophore [37, 38], by
combining the words ‘phoros’ meaning carrying and ‘pharmacon’ meaning drug.
Hence, a pharmacophore is ‘the molecular framework carrying the crucial features
accountable for a drug’s biological activity’. Since then, many groups have
attributed various definitions and meanings to this term based on their scientific
background and research view. IUPAC has officially defined a pharmacophore
model as [39]
An ensemble of steric and electronic features that is necessary to ensure the optimal
supramolecular interactions with a specific biological target and to trigger (or block) its
biological response.
However, a century’s research and development has expanded its circumstantial
meaning and application considerably. Due to their simple way of capturing and
representing the chemical features of compounds, pharmacophore models have
drawn the attention of the medicinal chemistry community in last few years as a
tool to screen the cig (chemistry) data [40]. Upon administration, when a drug/small
molecule enters the human body, it comes across thousands of proteins (receptors,
transporters, carriers, plasma proteins, etc.) to potentially interact with. But it
chooses to bind to only those proteins (targets) where the protein’s active site and
drug have compatible shape/size and the protein–drug interactions are energetically
favourable. Similarly, size/volume/shape and the chemical features of the residues
lining the binding pocket determine which type of small molecules it is able to bind.
Hence, the right size, correct shape and complementary chemical features are the
key factors for the protein–drug recognition to instigate a biological effect. The
central concept of pharmacophore is based on the perception that the molecular
interaction pattern of a group of compounds with their biological target can be
credited to a small set of common features complementary to the chemical features
Pharmacophore Modelling and Screening: Concepts, Recent …
27
these techniques, which will be of tremendous help for researches working in the
field of Mtb drug discovery [32].
Pharmacophore modelling is one of the enormously useful sub-areas of CADD
with diverse structure and ligand-based applications [33, 34]. Like docking, one of
the basic applications of pharmacophore models is virtual screening, but at a much
faster speed as compared to docking [33]. This approach can also be implemented
complementarily with docking and QSAR studies [18, 20]. Many studies use
pharmacophore models for target/off-target identification as well [35, 36]. In this
chapter, we basically focus on the in silico representation of the concept and the
varieties of ways of application of pharmacophore models in drug discovery projects.
2 The Concept of Pharmacophore
The term ‘pharmacophore’ has gained immense popularity in the field of medicinal
chemistry paralleled with computer-aided structure-activity relationship studies. In
1909, Ehrlich gave an introductory definition of pharmacophore [37, 38], by
combining the words ‘phoros’ meaning carrying and ‘pharmacon’ meaning drug.
Hence, a pharmacophore is ‘the molecular framework carrying the crucial features
accountable for a drug’s biological activity’. Since then, many groups have
attributed various definitions and meanings to this term based on their scientific
background and research view. IUPAC has officially defined a pharmacophore
model as [39]
An ensemble of steric and electronic features that is necessary to ensure the optimal
supramolecular interactions with a specific biological target and to trigger (or block) its
biological response.
However, a century’s research and development has expanded its circumstantial
meaning and application considerably. Due to their simple way of capturing and
representing the chemical features of compounds, pharmacophore models have
drawn the attention of the medicinal chemistry community in last few years as a
tool to screen the cig (chemistry) data [40]. Upon administration, when a drug/small
molecule enters the human body, it comes across thousands of proteins (receptors,
transporters, carriers, plasma proteins, etc.) to potentially interact with. But it
chooses to bind to only those proteins (targets) where the protein’s active site and
drug have compatible shape/size and the protein–drug interactions are energetically
favourable. Similarly, size/volume/shape and the chemical features of the residues
lining the binding pocket determine which type of small molecules it is able to bind.
Hence, the right size, correct shape and complementary chemical features are the
key factors for the protein–drug recognition to instigate a biological effect. The
central concept of pharmacophore is based on the perception that the molecular
interaction pattern of a group of compounds with their biological target can be
credited to a small set of common features complementary to the chemical features
Pharmacophore Modelling and Screening: Concepts, Recent …
27