Java Protein Dossier: HELP

 

General JavaProtein Dossier Area Help

Java Protein Dossier is an interactive presentation of important physical-chemical characteristics of the macromolecular structure described in PDB file. With a few mouse clicks a user can access data about chosen parameter, call other BLUE STAR STING modules or refine the search for a specific characteristic. By using color code scales for each residue of the sequence, JPD shows corresponding: temperature factor, solvent accessibility of the single chain (and also in complex with the other present chains in given PDB file), hydrophobicity, sequence conservation in a multiple alignment (relative entropy), double occupancies, reliability and histograms representing the atomic contacts. JPD also shows the identification of Interface Forming Residue (IFR) and their internal contacts. JPD offers information about electrostatic potential and curvature on protein surface. In addition, comparison of the Secondary Structure annotated by PDB, by DSSP and by Stride is presented. The JPD_HELP below is presented in the separate organizational units, so that a user is capable to quickly understand what is available in JPD DataBase and how to access this information, in addition to instructions which will show to a user what type of output he/she should expect. We relay much on the image summaries, rather than using the words.

INDEX

JPD Select HELP References Energy values for different contact types
Handling Local Files


This is a general area at the java window of JPD (click on any of the titles and you will get into more detailed explanation about highlighted areas):

 
Chain(s) and Parameter Area

InterFace Contacts (IFC)   Interface Residues/Ligand Pocket residues/Water Contacting residues/ Surface residues (IF - LP - WC - SF)
Density E. IFC  Unused Contacts  
Density E. ITC  Secondary Structure according to DSSP (SS_DSSP)
ResBoxes Multiple Occupancy
Prosite Conservation of the sequence according to HSSP  
Secondary Structure according to PDB (SS_PDB) Difference in Conservation between HSSP and STING´s calculation
Secondary Structure according to Stride (SS_Stride)   Hot-Spots
Temperature Factor Dihedral Angles  
Conservation of sequence according to STING´s SH2QS   Electrostatic Potential  [ ref. ]
Entropy Density  Curvature
Accessibility I  Density  
Pockets / Cavities   Order of Cross Link 
Hydrophobicity Order of Cross Presence 
Distances  Space Clash (5 categories) 
Sponge   ProTherm
Density E. IFC  Rotamers  
Contacts Energy  Color palette adjustment
InTernal Contacts (ITC)   

Parameter Names
IFC: InterFace Residue area Contacts - interatomic contacts established between residues belonging to two different chains facing each other. 
Density E.IFC: Energy Density of the IFC - The sum of Energies (calculated according to the table of energy values for each contact type) for the contacts established within a given sphere, among the residues belonging to two different chains facing each other, is calculated and then divided by the volume of the sphere. 
Contacts Energy - Sum of the Energies of contacts established among residues belonging to the same protein chain. (See the table of energy values for each contact type) 
Density E.ITC: Energy Density of ITC - The sum of Energies (calculated according to the table of energy values for each contact type) for the contacts established within a given sphere, among residues belonging to the same protein chain , is calculated and then divided by the volume of the sphere. 
ITC: Internal Contacts - Interatomic contacts among residues belonging to the same protein chain. 
ResBoxes: Residue Boxes - A single letter code is shown, representing the amino acids of the protein sequence which structure is inspected. The amino acid Boxes are color coded according to either STING_Paint code (1) or according to William Taylor (2) code.
IF: Interface area - Residues identified at the interface between two protein chains.
LP: Ligand Pocket Residues
WC: Internal, protein co-crystalized Water Contacting Residues
SF: SurFace residues (having contact with a solvent)
Prosite: Prosite pattern identification (3)
Unused Contacts - Each residue can make certain (max) number of contacts. The difference between the max number of contacts and the contacts established, is presented here.  
SS_PDB: Secondary Structure according to PDB (4) file annotation.
SS_DSSP: Secondary Structure according to DSSP(5) annotation.
SS_STRIDE: Secondary Structure according to STRIDE (6) annotation.
Mult. Occupancy -A presence of two or more sets of coordinates for the same atom/residue in the PDB file is due to the electron density map interpretation where the experiment registered a diffraction from the crystals freezing the same molecule but with the different space positions for a certain amino acid.
Temp. Factor: The temperature factor as annotated in a PDB file is presented.
Conserv. (HSSP): The Amino acid sequence conservation and reliability according to HSSP (7) data is presented here. The Evolutionary Pressure, calculated based on HSSP alignments, adequately prepared by BLUE STAR STING to be served as an input to Rate4Site (8) software, is also shown.  
Conserv.(STING) The Amino acid sequence conservation and reliability according to SH2Qs data is shown here. The Evolutionary Pressure, calculated based on SH2Qs alignments (adequately prepared by BLUE STAR STING) to be served as an input to Rate4Site (8) software, is also presented.  
Diff. Conserv. - The Difference in relative entropy, reliability and evolutionary pressure for HSSP and SH2Qs alignments is shown
Entropy Density - The sum of values is calculated for the relative entropy (according to HSSP (7) data) of the amino acids encountered within the sphere of a given radius, and then divided by the volume of that sphere.
Hot-Spots: This parameter indicates the existence of hydrophobic patches (9) at the surfaces of proteins.
Accessibility: The Amino acid accessibility is calculated according to SurfV (10) program. JPD shows 3 values: for the protein chain in isolation, for the protein chain in complex with the other chain (if) present in the PDB file and finally, a relative accessibility (the last one given by the table of absolute solvent accessible area for amino acids).  
Dihedral Angles - Dihedral angles are calculated according to the original work by Ramashandran (11) .  
Pockets/Cavities: Pockets/cavities are calculated using using two different algorithms: Pocket, which is part of the package ProShape; and NanoShaper.  
E. Potential - Electrostatic Potential is calculated using Delphi (12) program according to the modifications done by Walter Rocchia (13) and further adapted to JPD requirements (to be published)   [ ref. ] 
Hydrophobicity- The Hydrophobicity values are mapped according to the table with hydrophobicity values for 20 amino acids.
Curvature - The curvature values for each amino acid are calculated using the program SurfeRace (14).  
Distance - The Distance from the N-terminal amino acid Ca atom, C-terminal amino acid Ca atom and center of the protein mass point, is calculated from any given amino acid starting from its Ca atom.  
Density - The Density is calculated by the summation of atom mass for all atoms encountered within a sphere of a given radius (centered either at the CA [alpha carbon] or LHA [Last Heavy Atom] in the side chain of this residue), and then dividing it by the volume of the sphere.  
Sponge - Sponge is not an inverse of the Density! The Sponge is calculated by the summation of van der waals volumes for all atoms encountered within a sphere of a given radius (centered either at the CA [alpha carbon] or LHA [Last Heavy Atom] in the side chain for this residue), and then dividing it by the volume of the sphere.  
Order of Cross Link -The order of cross link is identified as a number of cross-links established among independent stretches of sequence (the size of which varies from 15, 20 to 30 Amino Acids). Cross Links are defined as contacts (any type from possible 5 classes: 1. Hydrophobic interaction, 2. Hydrogen Bonding, 3. Aromatic Stacking, 4. Salt bridging, 5. Cystein-bridging) established among residues that are far apart in the protein primary sequence, but are close in its 3D fold.  
Order of Cross Presence - Cross Presence is defined as presence within a probing sphere (centered at a given residue) of any residue that is far apart in the protein primary sequence from the central residue, but is close in its 3D fold. The order is identified as a number of such cross-presence encounters among independent stretches of sequence (the size of which varies from 15, 20 to 30 Amino Acids).  
Space Clash (5 categories) - The steric clash occurring among amino acids is reported here, measured by the "overlap factor", which is defined as the ratio of the distance between two atom centers to the sum of their van der Waals radii.  
ProTherm - ProTherm is a collection of numerical data of thermodynamic parameters such as Gibbs free energy change, enthalpy change, heat capacity change, transition temperature etc. for wild type and mutant proteins, that are important for understanding the structure and stability of proteins.
Rotamers - We have used the Rotamer Library presented in Lovell et. Al. to calculate and then evaluate how rare is the rotamer configuration for each residue in a given PDB file.  
Color palette adjustment - Although the color scale used to represent each parameter is fixed (e.g., gray scale, red to blue, red to green), the values associated with the beginning and the end of the color scale for each parameter can be changed. This is done to facilitate the visualization of the variation of the parameter in the residues sequence.

 

Local File Handling:

Generally, STING operates with both PDB public files and local files in pdb format. However, in order to handle properly STING_DB parameters for a local file, STING needs to pre-calculate those. Similarly, JPD can handle both public and local files and this can be done for a single structure and for two structurally aligned structures;
1. For the single structure, a user may submit a job to the STING Server and obtain in his/her e-mail box a msg with attached TGZ file, containing all parameters that the JPD can display and analyze.

2. For two structurally aligned files JPD can handle both two publicly available (PDB deposited) files or two local (non public) pdb formatted files. In this case a user needs to submit two local files to the STING server and obtain two TGZ files before doing structural alignment. See more details here.

 
References

 

1. Neshich, G., Togawa, R., Mancini, A. L., Kuser, P. R., Yamagishi, M. E. B., Pappas Jr., G., Torres, W. V., Campos, T. F., Ferreira, L. L., Luna, F. M., Oliveira, A. G., Miura, R. T., Inoue, M. K., Horita, L. G., de Souza, D. F., Dominiquini, F., Álvaro, A., Lima, C. S., Ogawa, F. O., Gomes, B. G., Palandrani, J. C. F., dos Santos, G. F., de Freitas, E. M., Mattiuz, A. R., Costa, I. C., de Almeida, C. L., Souza, S., Baudet, C. and Higa, R. H. (2003) STING Millennium: a Web based suite of programs for comprehensive and simultaneous analysis of protein structure and sequence. Nucleic Acids Research, 31:13, 3386-3392.

2. W.R. Taylor (1997) "Residual colors: a proposal for aminochromography". Protein Eng, Jul;10(7):743-746.

3. Falquet L., Pagni M., Bucher P., Hulo N., Sigrist C.J., Hofmann K., Bairoch A.(2002) The PROSITE database, its status in 2002 Nucleic Acids Res. 30:235-238.

4. Berman, H.H., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Res., 28, 235-242.

5. Sander, C. and Schneider, R. (1991) Database of Homology-Derived Protein Structures and the Structural Meaning of Sequence Alignment. Proteins: Struc., Func. and Genet., 9, 56-68.

6. Frishman, D. and Argos, P. (1995) Knowledge-Based Protein Secondary Structure Assignment. Proteins: Struc., Func., and Genet., 23, 566-679.

7.Schneider, R and Sander, C. (1996) The HSSP database of protein structure-sequence alignments. Nucleic Acids Res., 24, 201-205.

8. Pupko T., Bell R.E., Mayrose I., Glaser F. and Ben-Tal N. Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues. Bioinformatics (2002) Jul;18 Suppl 1:S71-7.

9. Philip Lijnzaad, Herman J.C. Berendsen and Patrick Argos.(1996) A method for detecting hydrophobic patches on protein surfaces. Proteins: Structure, Function and Genetics 26: 192-203.

10. Sridharan, S., Nicholls, A. and Honig, B. (1992) A new vertex algorithm to calculate solvent accessible surface areas. Biophys. J., 61, A174.

11. Ramachandran, G. N., Ramakrishnan, C. and Sasisekharan, V. (1963) Stereochemistry of polypeptide chain configurations. J. Mol. Biol., 7, 95-99.

12. B. Honig and A. Nicholls, (1995) Classical electrostatics in biology and chemistry. Science 268 1144-1149 .

13. W. Rocchia, S. Sridharan, A. Nicholls, E. Alexov, A. Chiabrera and B. Honig, (2002) Rapid Grid-based Construction of the Molecular Surface for both Molecules and Geometric Objects: Applications to the Finite Difference Poisson-Boltzmann Method, J. Comp. Chem. 23:128-137

14. Tsodikov OV, Record MT Jr, Sergeev YV. ( 2002) Novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature.J Comput Chem. Apr 30;23(6):600-9.

15. Radzicka, A. & Wolfenden, R. (1988). Comparing the polarities of the amino-acids -- side-chain distribution coefficients between the vapor-phase, cyclohexane, 1-octanol, and neutral aqueous-solution. Biochemistry 27, 1664-1670.