Perturbation response scanning specifies key regions in subtilisin serine protease for both function and stability

Abstract

Can one infer the amino acids of the enzymes that are responsible for the stability or the level of the catalytic activity by computationally experimenting on the inhibited enzyme in the enzyme–inhibitor complex? In this article, we answer this question positively both by designing molecular dynamics simulations and by devising coarse-grained methodologies on the subtilisin serine protease. Both methodologies are based on the cross-correlations of the fluctuations of the residues, obtained either by monitoring the trajectories from the simulation or by constructing the inverse Laplacian of the elastic network model, of the complex. A perturbation scanning is applied to the complex using these correlations. The results indicate that the two methods almost point out the same regions on the flexible of the enzyme. These regions are: (i) 50–61, (ii) 155–164 and (iii) 192–194, all of which are designated to be important by experimental studies in the literature.