The Shortest Path Map (SPM) analysis was performed using the MD simulations of HheC wild type and variant F12Y. For SPM calculation, the MD simulations are used to compute the inter-residue mean distance and correlation matrices. A simplified graph is created using both matrices, in which only the pairs of residues that show a mean distance of less than 6 Å along the MD simulation are connected through a line. The edge connecting both residues is weighted to the Pearson correlation value (dij=-log |Cij|). The residues with more correlated motions, will be connected through a shorter line. The generated graph is further simplified to identify the shortest path lengths. Following this strategy, the residues whose lines in the graph are shorter (i.e., with more correlated movements) and thus, play an important role in the conformational dynamics of an enzyme, are detected. Finally, the generated SPM graph is drawn on the 3D structure of the enzyme.