KIF is a computationally efficient approach, which can be executed on a standard laptop, with execution times for standard post-processing of MD simulation datasets typically requiring only several minutes or less. Here, we will describe the computational framework underlying KIF, and show its successful application to three model systems. The chosen model systems include a large, allosterically regulated, conformational change in a protein loop; a study on the impact of peptide binding on a neighboring protein domain; and characterizing how mutations alter the side chain conformations inside an enzyme active site for two engineered enzymes. Based on these showcase systems, it can be seen that our package KIF provides an efficient and largely automated approach to identify the key interactions and residues that modulate both subtle and large-scale conformational changes distributed throughout the protein, and even rank their relative contributions. Further, our approach provides users with the flexibility to describe any conformational change, however they see fit.