WISDOM: A Grid-Enabled Drug Discovery Initiative against Malaria - Grid Computing: Infrastructure, Service, and Applications - page 362

and different programs of the Amber distribution are responsible for per-
forming these steps:

• Preparatory phase

• Simulatory phase

• Analysis phase

Encoding these steps in separate programs has some important advan-
tages. First, it allows individual pieces to be upgraded or replaced with
minimal impact on other parts of the program suite. Second, it allows dif-
ferent programs to be written with different coding practices: LEAP is
written in C using X-window libraries, ptraj and antechamber are text-
based C codes, mm-pbsa is implemented in Perl, and the main simulation
programs are coded in Fortran 90. Third, this separation often eases port-
ing to new computing platforms: only the principal simulation codes
( sander and pmemd ) need to be coded for parallel operations or need to
know about optimized (perhaps vendor-supplied) libraries. The prepara-
tion and analysis programs are carried out on local machines on a user's
desktop, whereas time-consuming simulation tasks are sent to a batch
system on a remote machine; having stable and well-dei ned i le formats
for these interfaces facilitates this mode of operation.

14.3.3.3 Molecular Dynamics Refi nement and Rescoring Procedure

As shown in Figure 14.4, an automated multistep procedure for the
rei nement and rescoring of docking screening results was designed and

Docked
ligands
Mol2 files

Complex
topology

MM
input files

MM
structure

MM
input files

Out
RMSD

Refined
complexes

Sander
(MM)

Sander
(MD)

Sander
(MM)

MM-PBSA
MM-GBSA

Antechamber Leap Ptraj

Ligand
topology

Target structure
and ligand

Minimized
structure

MM
input files

Minimized
structure

Update of 3D
coordinates

Output free
energy scores

Complex preparation Complex refinement Output retrieving and rescoring

FIGURE 14.4 Schematic representation of the automated multistep rei nement and rescor-
ing procedure of the ligand-target complexes based on Amber. (From Rastelli, G. et al.,
Bioorganic and Medicinal Chemistry , 15, 7865-7877, 2007.)