3.1 Frequency distribution of hotspot and anchor residues
In all, calculations were made for a total of 5774 interface residues.
To our knowledge, this is one of the comprehensive study on hotspot
residues in PPI and PPepI. Out of 5774 residues, 3732 residues amounting
to 64.6% of the total dataset belong to hotspot categories having ∆∆G ≥
2 kcal/mol. This is suggestive of the fact that nature has remarkably
optimized a great majority (~65%) of the interface
residues in protein-protein complexes during evolution. This finding is
also in contrast to earlier notion that complex interface comprises only
few hot spot residues either isolated or in clusters [51]. The
frequency distribution is given in Table 2. Fig. 1 illustrates the
histogram of hotspots in PPI and PPepI categories. Altogether both
charged and polar residues contribute about 60% of hotspots. In the
histogram, the frequency curves drawn for both categories are in perfect
sync with a very minor difference at Gln, indicating the similar overall
tendency observed in PPI and PPepI. Arg, Tyr, Leu, Lys and Gln, are the
preferred hotspot residues at the PPI interfaces with Arg alone
accounting for over 10% in the frequency distribution. Met, His, Trp,
Gly and Cys are the least preferred hotspot residues with Cys presence
is mere 0.1 %. In contrast, Tyr, Leu, Arg and Ile are the most favoured
hotspot residues in PPepI category and Cys, Gly, Gln, Met and Trp are
the least preferred ones. Examining the trend, the PPI dataset is
characterized by the dominance of charged and polar residues followed by
hydrophobic residues, whereas PPepI dataset, the polar and hydrophobic
followed by charged residues predominantly occupy the frequency
distribution. The fact that negatively charged residues are not the ones
among preferred hotspot residues suggest that the electrostatic
complementarity is not a predominant factor in PPI and PPepI as well.
In PPI dataset, 249 anchor residues were recognized (37 weak, 118
moderate and 87 strong hotspots types; Supplementary. Table 1). In PPepI
category, 92 anchor residues were identified (12 weak, 46 moderate and
34 strong types; Supplementary. Table 2). Anchor residues mostly occur
for PPI dataset in moderate and strong types. The anchor residues
comprise of 8.3% of hot spot residues and about 5.3% of total residues
investigated in PPI and PPepI category. Anchor residues demonstrate
similar trend with Arg, Leu, Tyr Gln, Phe as the most preferred anchor
residue for PPI. For PPepI hydrophobic residue predominantly occupy at
the interface - Leu, Ile, Val, Phe, Tyr & Arg (Fig.1).