PatchFinder

An algorithmic tool for the identification of functionally important regions in proteins with known three-dimentional (3D) structure. The algorithm is based on the observation that evolutionarily conserved regions are often functionally important and based on the following three steps:

1. Assignment of an evolutionary conservation score¹ for each position in the protein.

2. Extraction of solvent accessible residues in the protein. This step is aimed on eliminating residues which are conserved due to structural constrains and are typically buried in the protein core.

3. Identification of the most significant cluster of conserved residues on the proteins' surface. This ML-patch is suspected to be the main functional site of the protein.

After the ML-patch was found the search procedure is continued for non-overlapping secondary functional sites with weaker conservation signal.

PatchFinder was examined on a dataset of 110 protein structures with annotated functional sites residues (del Sol Mesa et al., 2003). In addition we gathered a database of predicted functional sites for protein structures from the structural genomics consortia.

Required input:

PDB file:

Can be either supplied as a PDB ID or a path to your own PDB file.

Chain Identifier:

Specify a Chain Identifier (A, B, C, etc. in the corresponding field of the PDB file). If no chain is specified in the PDB file, type "NONE". 

Multiple Sequence Alignment (MSA):

This field is optional.

A Multiple Sequence Alignment in a text file with the query protein sequence. Clustal W and Fasta formats are accepted and the name of the query sequence within the alignment should be supplied.

The file should include at least five protein sequences.

Note: The query sequence should match the residues in the PDB file exactly.

Leaving this field empty, PatchFinder will try to construct an MSA in the same procedure used by ConSurf-DB, limiting the number of sequence homologs to 100.

Citing Information:

Please refer to:

Nimrod, G. Schushan, M. Steinberg, DM & Ben-Tal, N. (2008). Detection of Functionally Important Regions in "Hypothetical Proteins" of Known Structure. Structure 16, 1755-1763.

Nimrod, G., Glaser, F., Steinberg, D., Ben-Tal, N. & Pupko, T. (2005). In silico identification of functional regions in proteins. Bioinformatics 21, i328-i337.