Computational Drug Discovery and Design

Chapter 3

Practices in Molecular Docking and Structure-Based

Virtual Screening

Ricardo N. dos Santos, Leonardo G. Ferreira, and Adriano D. Andricopulo

Abstract

Drug discovery has evolved significantly over the past two decades. Progress in key areas such as molecular
and structural biology has contributed to the elucidation of the three-dimensional structure and function of
a wide range of biological molecules of therapeutic interest. In this context, the integration of experimental
techniques, such as X-ray crystallography, and computational methods, such as molecular docking, has
promoted the emergence of several areas in drug discovery, such as structure-based drug design (SBDD).
SBDD strategies have been broadly used to identify, predict and optimize the activity of small molecules
toward a molecular target and have contributed to major scientific breakthroughs in pharmaceutical R&D.
This chapter outlines molecular docking and structure-based virtual screening (SBVS) protocols used to
predict the interaction of small molecules with the phosphatidylinositol-bisphosphate-kinase PI3Kδ, which
is a molecular target for hematological diseases. A detailed description of the molecular docking and SBVS
procedures and an evaluation of the results are provided.

Key wordsAutodock vina, Drug discovery, Molecular modeling, Structure-based drug design, X-ray

crystallography

1 Introduction

Modern drug research and development (R&D) relies on the dis-

covery of low-molecular weight compounds that interact with

disease-related biological macromolecules (known as receptors or

molecular targets)inaselectiveway.Althoughthenumberofmolec-

ular targets that can be modulated by pharmacological agents is

estimated in approximately 10,000 gene products, only 4% of these

macromolecules are being investigated in drug discovery programs

[1]. In view of the potential that this unexplored space represents,

understanding the fundamentals that drive ligand–receptor interac-

tions is of critical importance to drug R&D [2]. In this context,

structure-based drug design (SBDD), that is, the use of structural

informationofmolecular targetstoimproveaspectsrelatedtoligand

binding, is a core approach in the pharmaceutical industry [3].

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_3,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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