2 Materials
In this section, we will describe the computational tools that are
required to generate the molecular target and database inputs,
develop the molecular docking simulations and visualize the results.
In general, this step-by-step guide assumes that the readers will
develop their molecular docking and SBVS studies on a Unix-like
computer operating system (e.g., any version of Linux Ubuntu or
Mac OS X or later).2.1 Initial Data
2.1.1 Molecular Target
3D Structures
Selecting a suitable 3D conformation of the molecular target, i.e.,
the spatial coordinates that define the relative position of each atom
within the structure, is a critical step in performing a molecular
docking study. One of the most commonly used sources of 3D
structural data for biological macromolecules, the Protein Data
Bank (PDB), incorporates structures determined by biophysical
methods such as X-ray crystallography, NMR spectroscopy, and
cryo-electron microscopy. PDB is freely accessible athttp://www.
rcsb.org/and will be used in this chapter to obtain the 3D struc-
ture of the molecular target [28].2.1.2 Small-Molecule
Database
The other required component for a molecular docking effort is the
3D structure of the small molecules to be evaluated. The structure
of these compounds can be obtained from distinct sources. Several
virtual compound databases are freely available, and the selection of
these collections depends on the goals of each drug discovery
project. For example, focused databases enclosing a specific chemi-
cal space are available for specific classes of proteins. Other collec-
tions concentrate on specific sources of compounds, for example,
the NuBBE database compiles various natural products from
organisms that are native to Brazil (http://nubbe.iq.unesp.br/por
tal/nubbedb.html)[29]. On the other hand, when no information
is available about known active ligands or when the investigated
target is known for interacting with different chemical classes,
general libraries containing widely diverse chemotypes can be
used. This type of collection generally contains hundreds of
thousands (or millions) of entries [30, 31]. Some examples of
these general and large repositories are the ChemSpider (http://
http://www.chemspider.com/) and ZINC (http://zinc.docking.org/)
databases [32, 33].2.2 Computational
Tools
In this section, we will introduce all programs that will be used in
this tutorial. Currently, there are numerous software programs and
tools available for use in each stage of the molecular docking
procedure. The tools enumerated here are well-established and
freely accessible programs (seeNote2).36 Ricardo N. dos Santos et al.