Abstract
Although the general mechanism for serine protease catalysis is well established, some questions still remain. For instance, the two enzymes, neutrophil elastase and cathepsin G, have a lot of structural resemblances; however, elastase degrades virulence factors, while cathepsin G does not. But their crystal structures are remarkably similar. Molecular dynamics simulations have been employed to study the two enzymes in solvent and probe their conformational differences.
The two protein structures do not have the same number of residues, which renders the measurement of the similarity over the duration of simulations problematic. In order to tackle the problem, we established and implemented a three-step-protocol: The Fréchet distance is used to superimpose the two protein structures, such that only internal motions will be probed in subsequent steps. The dynamic time warping algorithm and its penalty matrix is used to generate suitable pairs of amino acids between the two proteins. Lastly, a symmetrized version of the so-called Kullback-Leibler divergence is employed to quantify the difference and similarities between the two protein dynamics trajectories.
The approach showed a subtle difference in a specific residue in the two protein trajectories, which might explain the difference in specificity.