Value landscape of the contrast function for a large protein family illustrating the optimization process. The algorithm searches for the minimal value of the contrast function (a combinatorial entropy difference [Equation 6]) by systematic exploration of different clusterings (horizontal axis) and of different values of the granularity parameter A (vertical axis). The overall minimum (circle in red area, lower right, A = 0.68, value of normalized contrast function -187) determines which protein is in which subfamily and which residues contribute most to the specificity patterns across the subfamilies. Here, the value landscape (color contours, values normalized by the number of residues [283 columns] in the alignment) was computed for a multiple alignment of 390 protein kinases  with 0.0 <A < 1.0. Note that the lowest entropy value at A = 1 is far from the overall minimum, indicating the utility of this parameter.