Chapter 5
De Novo Design of Ligands Using Computational Methods
Venkatesan Suryanarayanan, Umesh Panwar, Ishwar Chandra,
and Sanjeev Kumar Singh
Abstract
De novo design technique is complementary to high-throughput virtual screening and is believed to
contribute in pharmaceutical development of novel drugs with desired properties at a very low cost and
time-efficient manner. In this chapter, we outline the basic de novo design concepts based on computational
methods with an example.
Key wordsADME, De novo ligand design, Drug discovery, Molecular docking, Molecular modeling,
Synthetic feasibility, VEGFR21 Introduction
The process of drug discovery has evolved manifold from adventi-
tious invention to more rational approaches. From the past three
decades computer-aided drug discovery/design (CADD) has
played a key role in the development of therapeutically important
small molecules [1, 2]. The explosion of the genomics data post-
sequencing and the three-dimensional crystallography structures of
various proteins (receptors/targets) has expedited the discovery of
medicinally significant small molecules. Structure-based drug
design and ligand-based drug design with the aid of different
computational techniques like virtual screening, molecular dock-
ing, molecular dynamics simulation, in silico adsorption, distribu-
tion, metabolism, excretion, and toxicity (ADMET) evaluations are
the primarily used methods for finding potential drug candidates.
De novo drug design is a computational technique wherein novel
molecular structures with desired pharmacological properties are
generated from the beginning or scratch. De novo in Latin literally
means “from new,” “afresh,” or “a new-fangled.” Besides finding
new molecules it is also used to produce novel molecular scaffolds
and bioisosteric equivalent for already determined or undesired
fragments. It not only generates chemical starting points/Mohini Gore and Umesh B. Jagtap (eds.),Computational Drug Discovery and Design, Methods in Molecular Biology, vol. 1762,
https://doi.org/10.1007/978-1-4939-7756-7_5,©Springer Science+Business Media, LLC, part of Springer Nature 2018
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