Protinfo FDWD server tutorial

Horst JA, Laurenzi A, Bernard B, Samudrala R. Computational shotgun multidisease multitarget screening. Polypharmacology 263-293, 2012.
Bernard B, Samudrala R. A generalized knowledge-based discriminatory function for biomolecular interactions. Proteins: Structure, Function, and Bioinformatics 76: 115-128, 2009.
Jenwitheesuk E, Horst JA, Rivas K, Van Voorhis WC, Samudrala R. Novel paradigms for drug discovery: Computational multitarget screening. Trends in Pharmacological Sciences 29: 62-71, 2008.

The Protinfo fragment-based docking with dynamics (FDWD) server module predicts putative atomic level structures of protein/ligand complexes. Given a protein structure in PDB format, a ligand structure in mol, mol2, or PDB format, and (optionally) a binding site location on the protein structure, this module will determine five different possible protein/ligand complex structures. For each complex structure, the module reports a score that assesses the goodness-of-fit, or likelihood, that the given pose is a physically realistic. Binding sites may be given in terms of the coordinates of the estimated centroid of the ligand, or in terms of the residues surrounding the binding pocket. If no binding site is given the server will predict the location of the binding site. Results are available on a web page with a unique URL known only to the user.

Protein:
Please upload a PDB file of the protein.
The protein structure should be similar to the bound conformation. However FDWD does account for binding-induced conformational change of the protein structure.

Ligand:
Please upload a mol, mol2, sdf, or PDB file of the ligand.
Upload any physically realistic ligand structure. The FDWD server accounts for conformational flexibilty of the query ligand.

Binding site:
Please give a comma delimited list of the indexes of the residues defining the binding pocket.
OR
Binding site:
Please upload a PDB file of a template ligand within the binding site.
OR
Binding site:
Please give the comma-delimited XYZ coordinates of the estimated position of the centroid of the binding site with respect to the protein structure.
OR
Binding site: Do not give any information about the binding site, and let the FDWD server predict the binding site location.
The FDWD server explores a set of binding poses subject to the constraint that the ligand lies within a sphere defined on the protein surface. This sphere represents the position of the binding pocket used by the docking algorithm. In order to correctly define this sphere, the user has the choice of 1) providing a set of residues that define the binding pocket, 2) providing pdb coordinates of a template ligand in the binding pocket (relative to the protein pdb coordinates), 3) providing an estimate of the binding pocket location, or 4) allowing the FDWD server to search the protein surface for the most likely binding site position.

Binding site radius:Å
Please enter a number between 10 and 30 for the radius (in Angstroms) of the search space sphere about the binding site centroid. The server will search for binding site poses within this radius. The default value is 10.
A wider search radius leads to a more comprehensive search, but also increases the search time.

Email(optional):
Please provide an e-mail if you would like notification when results are available.
Leave an e-mail address to receive notification when the server has results for your query

Download the example protein and ligand data here.

Sample output is available here.

Protinfo || Bioverse || Samudrala Computational Biology Research Group || protinfo@compbio.org