Computational Drug Discovery and Design

echo $nrj $fnam>>x_tmp;

i=‘expr $i + 1‘;

done

sort -n –k1 x_tmp>sorted_NRG

rm x_tmp

The output file sorted_NRG contains the sorted list of the

ligands, best on top. Inspect the intermolecular contacts and select

a number of candidates for the following steps. Then, run MD

simulation to validate the selected protein–ligand complexes.

Visualization of the OpenEye docking results can be done with

Vida, e.g., with the command "vida docked.oeb.gz". One can also

save the structures in the mol2 format (as one single file) to view

them with Pymol (as individual models).

3.6 Validation
of Complexes by MD
Simulations

1. Putative complex structures resulting from docking studies
   should be validated from the point of view of their stability.
   The MD simulation performed even for a relatively short
   stretch of time (10–20 ns) can give a wealth of information
   about the behavior of the ligand within the binding site, as well
   as about the nature of the intermolecular contacts.
   The preparation of input data for MD simulation of com-
   plex structures is similar to the procedure described above for
   the receptor. The difference is that a new molecule (ligand) has
   to be added to the system and we need its topology. In general,
   it will require the use of a different force field. In what follows
   we assume that ligands are small organic molecules which can
   be treated by the general Amber force field (GAFF) [54].
   We start with a PDB file of a ligand molecule. Make sure
   that the ligand is protonated. Use the antechamber utility to
   generate the first of the tleap input files:

antechamber –nc 0 –rn LIG –I lig.mol2 –fi mol2 –o lig.prep \

-fo prepc –c bcc –s 2

The meaning of the options is as follows: ns¼net charge, rn¼

residue name, i¼input file, fi¼format of the input file, o¼output

file, fo¼format of the output file (prepc or prepi), c¼charge

model, s¼output verbosity. When the lig.prep file is ready, we

check if all force field parameters are available:

parmchk -i lig.prep -f prepc -o lig.frcmod

The contents of the output frcmod file should be examined,

and if problems occur, they should be fixed before continuing (see

Note 9).

Molecular Dynamics in Virtual Screening 165