Protein flexibility and signal propagation in homo-oligomeric enzymes

Abstract

In a cell, enzymes dynamically regulate all types of cell metabolism. It is known that enzymes are often in a homo-oligomeric state. Dynamic flexibility of catalytic sites, as well as efficient signal propagation between them, is critical for a protein to function properly. However, it is difficult, if not impossible, to study the protein dynamics using conventional all-atom molecular dynamics (MD) simulation method because it requires a prohibitively long simulation time. This difficulty is more severe for the oligomeric proteins because of their large size and relatively slow dynamics. Fortunately, however, simplified dynamics tools are emerging in recent years. One of the popular methods is the Gaussian network model (GNM), which successfully describes protein equilibrium dynamics by modeling a protein structure as a collection of the harmonically coupled residues. By using GNM, collective normal modes of protein can be easily calculated regardless of the size of proteins, from which information relevant to protein function such as dynamic flexibility of residues and the signal propagation between residues can be extracted. In this paper, we studied how oligomerization influences We first studied the dynamic flexibility of catalytic sites in homo-oligomer enzymes. We found that these flexibilities are closely related with the number of subunits and the structural stability of homo-oligomer enzymes. And then, we calculated the signal propagation between catalytic sites in the different domain in homo-oligomer enzymes. Our results indicate that these signals depend on physical distances between them and the oligomeric configurations; if two catalytic sites was close, then the signal is slow, and vice versa.