Amino Acid Pairs in Proteins Figure 8. Occurrence of pairs between positive charge residues as a function of distance between any two residues and the solvent accessibility of the shell where the pair is found. As explained in Figure 6, absolute (panels A, C and E) and ratio (panels B, D and F) plots are displayed for each pair. A total of 3412 Lys-Lys pairs (panels A and B), 7574 Arg-Arg pairs (panels C and D), 3747 Arg-Lys pairs (panels E and F) were analyzed. The intensity map is color coded like described in Figure 4. doi:10.1371/journal.pone.0025638.g008 structural location within a particular protein structure, as displayed in Figures 10A, B and C. Further constraints were used when searching for structures containing these pairs: Arg residues should be within a sequence distance larger than 4 and could be located in coil elements (Fig. 10A), in a-helix (Fig. 10B) or in b- strands (Fig. 10C). Therefore the data displayed by ProPair in Figure 10 is a result of querying the data cube using a combination of 8 dimensions using the programs ProPack and ProPair. The 8 dimensions are: AA1- Arg, AA2- Arg, 10,SA#30%, D- 3.3–3.8 A˚, SS1- coil, SS2- coil, CL- all, SD.4. The displayed data shows the structural reasons that justify the presence of unexpected buried and spatially close Arg-Arg pairs: these positively charged pairs can bind a phosphate group and at the same time be involved in a complex salt bridge network with other titratable residues, this way Figure 9. Pair preferences for particular secondary structural elements. A) Secondary structural elements preferred by Lys and Asp pairs with a sequence distance of 2 and with inter-residue distances between 2.3–3.8 A˚ in protein shells with 20,SA#40%. Lys and Asp prefer to be located in b-sheets or in coil structures. A typical local 3D structure around a Lys-Asp pair (displayed in yellow and blue, respectively) with the characteristics depicted by the beta-beta peak is displayed. Distances between functional groups are displayed. B) Secondary structural elements preferred by Lys and Asp pairs with a sequence distance of 4 and with inter-residue distances between 2.3–3.8 A˚ in protein shells with 20,SA#40%. Lys and Asp (displayed in yellow and blue, respectively) prefers to be located exclusively in a-helices. A larger salt bridge network involving two additional residues (Asp 59 and Lys 62, displayed in brown and purple, respectively) located in a nearby a-helix is displayed. doi:10.1371/journal.pone.0025638.g009 PLoS ONE | www.plosone.org 15 December 2011 | Volume 6 | Issue 12 | e25638