Computational Drug Discovery and Design

4 Virtual Screening

In this section, we will use multiple ligands in the molecular dock-

ing simulation to perform an SBVS protocol. Several compound

libraries covering a wide range of structural and physicochemical

features are available on the web. In this example, we will use the

NuBBE database to predict likely ligands for PI3Kδ.

4.1 Obtaining
the Compound Library

The front page of the NuBBE database (http://nubbe.iq.unesp.

br/portal/nubbedb.html) shows a form that allows the user to

search compounds based on specific characteristics (e.g.,substruc-

ture, physicochemical properties, and source). First, we will select a

subset of compounds to be screened from the database. Leaving all

fields in the form blank, selectIsolated from a microorganismin the

source section, and click onSearch compound(s)located at the

bottom of the page. This procedure will generate a list of entries,

each one containing a set of information, such as the accession

code, structure and chemical class. Download the file containing

all the 3D molecular structures of this selected group of com-

pounds by clicking on themol2link in the results section. Extract

and copy the generatedmol2files to a new folder named VS inside

your workingDockingdirectory. Next, open a terminal in this

folder.

4.2 Running
the Virtual Screening

The Chimera-Autodock Vina interface supports docking studies

using a single molecule at a time. To perform the SBVS with the

dataset containing multiple molecules downloaded from NuBBE,

we need to run Autodock Vina independently. First, generate a

configuration file for the docking parameters by creating a text

file using any editor (e.g., gedit) and copying the following data

inside:

center_x = -6.612

center_y = -13.356

center_z = 23.712

size_x = 15.00

size_y = 15.00

size_z = 15.00

energy_range = 3

exhaustiveness = 8

num_modes = 1

Note that these parameters are the same as those inserted in the

Chimera interface while running the molecular docking analyses

(Fig. 2a); however, only one conformation for each molecule

(num_modes¼ 1 ) will be generated in this SBVS protocol. Save

this new file asconf.txtin the current folder (VS). Next, use the

following script to automate the docking procedure for all mole-

cules. To do this, create another text file, and copy the following

data inside:

Molecular Docking and Structure-Based Virtual Screening 45