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In-Depth Information
In MoSGrid multiple workflows are implemented based on GROMACS (Hess
2008) covering variants of this generic protocol. The workflows are designed to
meet the needs of expert users as well as to guide beginners through the complex
task of simulation system generation. When submitting a workflow the validity of
the con
guration is checked against the corresponding MSML dictionary to ensure
a meaningful simulation. The progress of the calculation can be followed through
the monitoring tab of the MD portlet. For expert users a very basic but powerful
workflow is provided. It allows the upload and submission of a self-prepared binary
GROMACS topology (topol.tpr), taking maximum advantage of the computing
resources available through MoSGrid.
11.4.3 Docking
Molecular docking deals with the stability of molecular complexes, mostly with the
energetical and geometrical evaluation of protein receptors and small-molecule
ligands. This simulation technique is widely applied in the research
field of drug
design to perform virtual high-throughput screening of potential drug candidates.
Over the last decades a plentitude of docking applications have been released. They
can be categorized by their placement method, i.e., the algorithm used to create the
correct pose of a ligand bound to its receptor. Autodock Vina, for example, takes
advantage of precomputed grids for all kind of probe groups to calculate interac-
tions. The CADDSuite also relies on precomputed grids, but uses a multi-greedy
approach for ligand placements. Furthermore, the suite is highly modular and
contains a variety of tools for pre- and post-processing. FlexX (Fuhrmann 2006)
relies on the decomposition of the ligand into fragments and then uses a multi-
greedy heuristic to reconstruct the ligand inside the binding site. All three appli-
cations are available through a dedicated docking portlet offered by MoSGrid. Their
individual workflows rely on the preparation tools of the CADDSuite. This includes
explicitly the assignment of reasonable protonation states for the amino acid side
chains within the binding pocket of the receptor. Furthermore, the ligands
three-
dimensional structure has to be created in such a way that the topology and ste-
reochemistry are preserved. Given that there are a multitude of structural formats,
the docking portlet has the capability to
'
filter the input in order to ensure a valid
input dataset, which is also stored as MSML
file. The key challenge for docking
large ligand libraries in a grid environment is the sensitive splitting and distribution
of ligands on remote DCIs and consequently to individual compute cores. The
MoSGrid docking workflows for FlexX, Autodock Vina and the CADDSuite
handle this issue through the combination of the CADDsuite tool LigandFileSplitter
with a gUSE generator node. The user may set within the portlet whether the given
ligand library is split evenly into a given number of chunks, or if each chunk shall
contain a given number of ligands. These chunks are then further processed and
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