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PESDserv - Help

The server
You can obtain a list of protein-ligand binding sites, ranked in order of their similarity to an uploaded ligand bound site. The server uses a surface representation of binding sites for similarity computation and compares the uploaded binding site to a total of 106,796 ligand bound site surfaces extracted from the PDB. The surfaces used are property-mapped Gauss-Connolly surfaces generated in MOE (Molecular Operating Environment, Version 2007.09, Chemical Computing Group, Inc.). Water molecules were not included for generating the site surfaces in the database.

The algorithm
The server implements the Property Encoded Shape Distributions algorithm for calculating the global similarity in surface shape and property distributions on the surface of ligand binding sites of proteins. The algorithm appears in the following publication:

Das, S.; Kokardekar, A.; Breneman, C. M. Rapid Comparison of Protein Binding Site Surfaces with Property Encoded Shape Distributions. J. Chem. Inf. Model. 2009, 49, 2863-2872.

Usage
Upload a ligand file and a protein file in PDB format. The ligand and the protein should be in the same coordinate space, since the location of the ligand is used to generate the ligand binding site of the uploaded protein (at 4.5 Angstrom to the ligand atoms). Anything that is present in the protein file will be treated as protein. Do not leave a copy of the uploaded ligand in the protein file. The ligand should be separated from the protein file before uploading. Water molecules should not be normally included in the protein file. Select the option for the distance metric: L1 (Manhattan), L2 (Euclidean), or chi-squared (recommended), the number of top ranks desired in the output page and click on "Submit Query".

Example case

We will use the ligand bound site of mutant estrogen nuclear receptor as a query:

1. Download the PDB entry 1qkt from the RCSB-PDB website. To download click here.

2. Split the 1qkt.pdb file into a protein file and a ligand file. Open the 1qkt.pdb file in notepad or any text editor and save atoms 1 through 1981 as protein.pdb and 1982 through 2001 as ligand.pdb (atoms 1982 through 2001 is the estrogen ligand whose binding site we want to compare). Click to download: protein file after splitting | ligand file after splitting.

3. Point to the ligand file and the protein file by clicking on the respective Browse buttons.


4. Choose distance metric and number of ranks to return.

5. Click on Submit Query.

After submission, the screen will automatically refresh until the results page is obtained.


Reference
For further details and citing the server:
Das, S.; Krein, M.; Breneman, C. M. PESDserv: A server for high-throughput comparison of protein binding site surfaces. Bioinformatics, 2010, Epub Ahead of Print. DOI: 10.1093/bioinformatics/btq288

Grants
National Institutes of Health, Grant: 1P20 HG003899 and Rensselaer Polytechnic Institute Fellowship to Sourav Das.

Contact
Professor Curt Breneman

Dr. Sourav Das

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