Università degli Studi di Milano Dipartimento di Scienze Farmaceutiche “Pietro Pratesi”. GriDock: An MPI-based software for virtual screening in drug discovery. Alessandro Pedretti. Database of molecules. Set of molecules. Database of molecules. Database filter. Experimental assay.
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Dipartimento di Scienze Farmaceutiche “Pietro Pratesi”
GriDock: An MPI-based software
for virtual screening in drug discovery
Set of molecules
Database of molecules
What is the virtual screening ?
The 3D structure of the biological target is unknown and a set of geometric rules and/or physical-chemical properties (pharmacophore model) obtained by QSAR studies are used to screen the database.
Structure-basedIt involves molecular docking calculations between each molecule to test and the biological target (usually a protein). To evaluate the affinity a scoring function is applied. The 3D structure of the target must be known.
Ligand – receptor complex
GriDock – Main features
Ligand – receptor complexes
How GriDock works
Conversion to PDBQT
to AutoDock 4
How VEGA works with GriDock
AMBER force field
Calculation of charges
Search of flexible torsions
GriDock multi-threaded version
GriDock main thread
Symmetric multiprocessing (SMP) provided by pthread library or Windows APIs
Mutex controlled access
GriDock MPI master node
GriDock MPI version
To perform a virtual screening with GriDock, you need:
The Citrus tristeza virus case
ssRNA (+) – 5’ prot.
To the refinement
The RdRp model
The crystal structure doesn’t exist and a homology modeling procedure was performed:
Rough 3D structure
Side chains add
for the screening
Calculation of charges
Apolar hydrogens remove
Mapping the active site
AutoGrid 4 run
Grid map files
Calculation of the grid maps
AutoDock requires pre-calculated grid maps to evaluate the total interaction energy between the ligand and the target macromolecule.
To do it, we used the script included in the VEGA ZZ package:
All test databases in SDF format were downloaded from http://ligand.info:
The total number of docked ligands is: ~1,000,000
The top ranked ligands contains in their structure one or more sulfurs.
Sulfonic acid derivatives.
These compounds are know to be potent inhibitors of the HIV reverse transcriptase. Some of them are naphtalen polysulfonic acids developed as Anti-HIV (Anti-HIV NCI database).