2.2.1 AutoDock Vina AutoDock Vina, one of the most cited molecular docking software
programs, combines an efficient stochastic conformational search
algorithm and accurate and well-rated force-field-based and empir-
ical scoring functions [34]. The combination of its efficacy and
suitability for parallelization results in a low computational cost
making this program an attractive option for performing SBVS
studies against large compound libraries. Executable files and theo-
retical details about AutoDock Vina and its installation and use can
be accessed athttp://vina.scripps.edu.
2.2.2 BKChem In addition to chemical databases, novel molecules can be drawn
from scratch using chemical drawing suites. Frequently, a series of
molecules known to be active against an investigated molecular
target are used as references to design novel compounds. BKChem
is an open-source chemical drawing program that provides a user-
friendly interface for generating 2D structures that can be used as
an initial sketch to build 3D conformations. The program is able to
assign important features such as specific protonation states and
chirality and can be accessed athttp://bkchem.zirael.org[35].
2.2.3 Open Babel This toolbox is an open and collaborative resource broadly used to
interpret and interconvert a variety of chemical file extensions
[36]. Extremely convenient for converting chemical formats that
are not compatible with distinct programs, this platform allows for
a smooth and straightforward workflow along the molecular dock-
ing process. Open Babel includes other useful functionalities such
as filtering and searching routines, as well as generation of 3D
coordinates and prediction of protonation states. This resource is
available athttp://openbabel.org.
2.2.4 UCSF Chimera UCSF Chimera is a molecular modeling software for visualization
and analysis of a wide range of data related to biomolecular systems
[37]. This software is able to handle 3D structures of macromole-
cules and small-molecule ligands, density maps, sequence align-
ments, molecular docking results, conformational ensembles, and
molecular dynamics trajectories. This resource is also suitable for
generating high-quality illustrations and animations for scientific
purposes. UCSF Chimera can be downloaded athttp://www.cgl.
ucsf.edu/chimera.
3 Methods
To perform the molecular docking protocol described herein,
phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3Kδ) was
selected [38–40]. PI3Ks play a key role in the regulation of several
signaling pathways related to fundamental cellular processes such as
differentiation, proliferation, metabolism, motility, and cellMolecular Docking and Structure-Based Virtual Screening 37