Brief Module Description
MSSP (Multiple Structure Single Parameter 2D Plot) is a BlueStar STING module that offers a complementary method for the analysis of mutants or any set of structurally similar proteins. It allows the creation of graphical representations (2D Plots) of protein descriptors that characterize a shared loci on structurally aligned protein chains. The global structural aligmnent can be obtained by two different programs: MUSTANG[1] and MAMMOTH-mult[2].
It's important to emphasize that MSSP is aimed to be used as tool for protein chains analysis, one chain at the time from each selected PDB file. However, a user might be able to edit a PDB file and join 2 or 3 or more chains into a single chain, and in that way consider changes among multichain structures on the whole protein level. MSSP is not yet dealing with ligand properties as those need separate calculations and we are not offering such data at the moment.
Protein Descriptors
MSSP uses a small fraction of the protein descriptors from the BlueStar STING database, which covers all proteins in the PDB and is updated weekly. Currently the BlueStar STING database has over 1050 descriptors that are provided in a residue-by-residue manner.
A short description for the main descriptors used by MSSP follows:
| BlueStar STING Protein Descriptors used by MSSP | |
|---|---|
| Temperature Factor | The temperature factor (TF) as annotated in a PDB file. The Temperature Factor indicates the level of the mobility for the atoms in the crystal. BlueStar STING indicates 4 values: TF at the carbon alpha (CA), TF at last heavy atom (LHA), Max encountered TF among all atoms belonging to the selected amino acid and finally, the average TF value. |
| Dihedral Angles | The PHI and PSI angle of the main chain. |
| Curvature | The curvature values for each amino acid residue are calculated using the program SurfeRace[3]. SurfeRace calculates the curvature value for each atom. The curvature of residues is the average of the surface atoms curvature. |
| Distances | The Distance from the N-terminal amino acid carbon alpha, C-terminal amino acid carbon alpha and center of the protein mass point, are calculated from any given amino acid starting from its carbon alpha. |
| Density | A probe sphere of varying radius (from 3 to 7 Å) is centered either at the carbon alpha (CA) or the last heavy atom (LHA) in the amino acid residue side chain. The masses of the atoms are summed and divided by the probe volume |
| Sponge | This attribute is similar to the density definition in calculation, but instead of using the atomic masses, the volumes of the atoms are subtracted from the probing sphere volume and normalized. |
| Contacts | BlueStar STING identifies all potential intra-protein chain (internal) and inter-protein chain (interface) contacts by classifying amino residue atoms in groups according to both their electrostatic behavior and position in the amino acid (main or side chain). |
| Contacts Energy | Atoms or residue pairs are associated with the following energy values: hydrophobic interaction = 0.6 kcal/mol; aromatic stacking = 1.5 kcal/mol; hydrogen bond = 2.6 kcal/mol; salt bridge = 10.0 kcal/mol; and cysteine bridge = 85.0 kcal/mol. |
| Energy Density | The sum of energies for the contacts established within a probe sphere of varying radius (from 3 to 7 Å) is calculated and then divided by the volume of that sphere. The probe can be centered either at the carbon alpha (CA) or the last heavy atom (LHA) in the amino acid residue side chain |
| Unused Contacts Energy | The entire PDB is screened for the maximum contact energy of each amino acid type. This maximum value is subtracted from the contact energy of each particular amino acid residue. The resulting value is considered the amino acid residue contact potential, which is yet to be established. |
| Electrostatic Potential | BlueStar STING uses a modified version of DelPhi software for high-throughput calculation[4]. DelPhi solves the Poisson-Boltzmann equation for each group of fixed charge points that constitutes each type of amino acid residue in a protein. |
| Conservation | Sequence conservation and reliability according to HSSP and SH2QS (MyHSSP)[5]. |
| Accessibility | In order to calculate protein surface accessibility, BlueStar STING applies the rolling sphere algorithm as implemented by the software SurfV[6]. For protein complexes, the amino acid-accessible surface for each individual chain (accessibility in isolation) and for the complete PDB (accessibility in complex) are calculated. Amino acid residues that undergo changes in their accessibility upon protein-protein complex formation are referred to as IFRs. |
| Hydrophobicity | BlueStar STING uses the Radzicka and Kyte-Doolittle amino acid scales of hydrophobicity weighted by the amino acid relative accessibility as a definition of amino acid hydrophobicity. |
References
- Konagurthu, A. S., Whisstock, J. C., Stuckey, P. J., & Lesk, A. M. (2006). MUSTANG: a multiple structural alignment algorithm. Proteins: Structure, Function, and Bioinformatics, 64(3), 559-574.
- Lupyan, D., Leo-Macias, A., & Ortiz, A. R. (2005). A new progressive-iterative algorithm for multiple structure alignment. Bioinformatics, 21(15), 3255-3263.
- Tsodikov, O. V., Record, M. T., & Sergeev, Y. V. (2002). Novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature. Journal of computational chemistry, 23(6), 600-609.
- Rocchia, W., & Neshich, G. (2007). Electrostatic potential calculation for biomolecules-creating a database of pre-calculated values reported on a per residue basis for all PDB protein structures. Genet Mol Res, 6(4), 923-936.
- Higa, R. H., Cruz, S. A., Kuser, P. R., Yamagishi, M. E., Fileto, R., Oliveira, S. R., ... & Neshich, G. (2006). Building multiple sequence alignments with a flavor of HSSP alignments. Genet. Mol. Res, 5(1), 127-137.
- Sridharan, S., Nicholls, A., Honig, B. (1992). A new vertex algorithm to calculate solvent accessible surface areas. Biophys. J., 61, A174.