5.4 Comparative Modeling: Model Validation

It is imperative to check the validity of any comparative model, first in computro, later by experiments. It would be foolish to trust blindly a model. The first step is of course to check the quality of the 3D structures used as a template for the comparative model. Reports on all PDB structures have been compiled in PDBreport (http://www.cmbi.kun.nl/gv/pdbreport/).

New structures and 3D models can be checked with the Biotech Validation Suite for Protein Structures. Three different software packages can be run on the server:

• PROCHECK: checks Covalent geometry, Planarity, Dihedral angles, Chirality, Non-bonded interactions, Main-chain hydrogen bonds, Disulphide bonds, Stereochemical parameters.
• SurVol: The atomic volume check calculates for each atom in the structure the atomic volume. It compares these volumes with a pre-computed average for each atom type. This comparison results in a Z-value for each buried atom.
• WHATCHECK: checks bond angles, bond lengths, buried Hydrogen Bond Donors, Bumps, chain names, Peptide Plane Flips, Chiral Handedness, HIS GLN ASN side chain conformation, Nomenclature, side chain planarity, proline puckering, Quality, Side-chain Rotamers, Symmetry Check, Torsion angles, water clusters, atomic occupancy.

In addition, a 3D-1D profile verification can shed light on dubious areas in the structure. The 3D-1D server is at UCLA-DOE Structure Evaluation (http://www.doe-mbi.ucla.edu/Services/Verify_3D/).

One of the most important checks for any 3D protein model is the Ramachandran plot. Any non-Gly residue outside of the 'allowed' zones should be carefully inspected.