Computational Drug Discovery and Design

#! /bin/bash

mkdir results

for i in *.mol2; do

a="${i%.*}"

obabel -imol2 $i -opdbqt -O $a.pdbqt

vina --config conf.txt --receptor ../*.receptor.pdbqt --

ligand $a.pdbqt --out results/$a.docked.pdbqt

done

rm *.pdbqt

cat results/*.docked.pdbqt>all.docked.pdbqt

Save this new file as vs.shin the VS folder in which the com-

pound dataset and the fileconf.txtare located. Finally, run the

screening by executing the above-generated script with the follow-

ing command:

bashvs.sh

The calculations should take several minutes. At the end of the

process, the Auto Dock Vina algorithm will create a folder named

resultscontaining the docked conformation for each molecule eval-

uated. In addition, this algorithm will generate a single file contain-

ing all docking results concatenated in a file namedall.docked.pdbqt.

To analyze these results, go to Chimera, and open the receptor

structure saved in theDockingfolder. To do this, go toFile!

Open, and choose the filereceptor.mol2. To visualize the SBVS

results using Chimera’s ViewDock tool, go toTools!Surface/

Binding Analysis!ViewDock, and open the concatenated fileall.

docked.pdbqt. Similar to the visual analyses performed for idelalisib,

a table with all predicted conformations and their energy values

allows the selection and exploration of each docking solution. The

Hbondstool can be used again to identify the hydrogen bonds

formed in each ligand–receptor complex.

5 Further Considerations

Despite the capabilities of molecular docking in predicting the

conformation of a ligand in the target binding site, the calculated

interaction energy should not be considered a reliable estimation of

ligand–receptor affinity. Once docking programs use simple physi-

cal models that do not consider nonclassical phenomena (entropic,

desolvation, and quantic effects), their estimations of binding ener-

gies are rarely accurate. However, because the accuracy of this

measure is equal for all molecules in an SBVS study, the relative

energy ranking among conformations is valid and useful for distin-

guishing ligands with a high probability of binding to the target in

experimental tests.

Another fundamental aspect that should be considered when

searching for potential candidates for experimental evaluation is the

46 Ricardo N. dos Santos et al.