PURPOSE: This protocol is designed to compare the binding site of one (reference) protein with putative binding sites in similar aligned proteins. Per residue RMSD values and chi values are reported for the aligned binding site residues.
The Selection Method parameter provides the option to define the binding site as a set of residues OR let the protocol determine the residues from a selected Ligand and cutoff distance. When:
Selection Method = Reference Ligand
- collects all residues within the specified radius of the selected Reference Ligand.
- and considers these the reference binding site residues
- Note, the selection of the Reference Ligand also determines which protein molecule will be the Reference Molecule against which all other molecules are compared
Selection Method = Reference Binding Site Residues:
- defines the binding site residues as a user specified group or selection
The protocol then:
♦ (optionally) superimposes the structures based on the Input Sequence Alignment using either:
- all aligned residues OR
- only the binding site residues defined in the Reference Molecule
- backbone atoms within the specified residues OR
- C-alpha atoms within the specified residues
♦ calculates rmsd of residues aligned to the binding site residues:
- sidechain, backbone, calpha and all-protein atom rmsds reported
♦ calculates chi angles of the binding site residues of the Reference Molecule and all residues aligned to them
♦ lists the aligned residues, reference residues, calculated rmsd values and chi angles in a csv file for each aligned protein
♦ writes an output .msv file containing:
- the superimposed structures (if superimposition is performed)
- new Molecule level groups: "Ref BSite Residues" (for the Reference Molecule) and "Aligned to BSite Residues" (for each of the aligned Molecules)
USAGE: This protocol can be launched from both the Discovery Studio and Pipeline Pilot clients. To install in Discovery Studio only, go to the Protocol Explorer, right-click over the folder you want to add the protocol to, choose Import, navigate to the location of the Analyze Protein-Ligand Complexes (Compare Binding Sites).xml file and enter it as the File Name.
REQUIREMENTS: Discovery Studio Embedded Collection
KEYWORDS: binding site analysis, alignment, rmsd, side chain, chi values
DISCLAIMER: This custom protocol is compatible with Discovery Studio 2.1 and Pipeline Pilot Server versions 6.1.6 and 7.0.1 (SES). It is provided "as is" and is NOT supported by Accelrys nor is it warranted for any purpose whatsoever. The user assumes responsibility for any malfunctions or bugs.
