It is noteworthy that the above notion of interacting bit-patterns is new compared to our previous work, where two bit-patterns are associated if their distance in the 2D contact map space is below a certain threshold. This can be misleading in the context of protein folding analysis. As demonstrated in Figure 8, the two bit-patterns-BP #1 and BP #2-are only 2 amino acids away in the 2D contact map. However, they can be relatively far apart in 3D. On the other hand, although the bit-patterns BP #2 and BP #3 are relatively far apart from each other in the 2D contact map, they are close to each other in 3D. Therefore, measuring the distance between bit-patterns in the actual 3D conformation is more robust with respect to capturing potential interaction among local motifs.