Amino Acid Pairs in Proteins Figure 6. Occurrence of pairs between opposite charge residues as a function of the spatial distance between them and the solvent accessibility of the shell where the pair is found. The so called ‘‘Absolute’’ plots display the number of contacts found and the ‘‘Ratio’’ plots are the ratio between the data in the absolute plots and the corresponding data found in the reference dataset of randomized structures. Figures 6A and 6B report the contacts found between 7784 Lys-Asp pairs. Figures 6C and 6D report the contacts found between 9649 Arg-Asp pairs. The intensity map is color coded like described in Figure 4. doi:10.1371/journal.pone.0025638.g006 displayed in Figure 10E (displayed in yellow and blue. 3.6 A˚ apart) belongs to 2SCP.pdb, a sarcoplasmic calcium-binding protein. Asp16 is located in a loop region and Asp27 is located in an a- helix. Two additional Asp residues are also involved in Ca2+ binding (Asp18 and Asp20, colored brown). Discussion In the introduction we have argued for a total of 8 dimensions spanning the protein fold space. These 8 dimensions may be orthogonal to one another, or each dimension may be linear combinations of two or more of the other dimensions. For example the sequence length will define the size of the protein and thereby also influence the number of both solvent exposed and buried residues. No matter of how many independent dimensions we can define, only two dimensions are usually displayed simultaneously. A third dimension can be added in terms of a color. The bioinformatics approach presented in this paper allows the user to carry out hyper dimensional analyses of amino acid pair interactions and their distribution in proteins with an incorporated graphical analysis tools, making possible the visualization of any conceivable combination of the 8 dimensions for each amino acid pair as projections in 1D, 2D and 3D plots. The data cube obtained by ProExtract can be queried using the programs PLoS ONE | www.plosone.org 11 December 2011 | Volume 6 | Issue 12 | e25638