Molecular dynamics simulation integrating study for Cr3+-binding to arginine kinase

Abstract

We simulated the 3D structure of arginine kinase from Exopalaemon carinicauda (ECAK) on the basis of homology modeling. Computational molecular dynamics simulations between ECAK and Cr3+ were conducted to elucidate the functional role of Cr3+ on ECAK structure and catalysis. As a result, the binding mechanism of Cr3+ to ECAK along with binding sites and structural changes were predicted. To confirm the simulation results, kinetic studies of Cr3+-mediated aggregation of ECAK were subsequently conducted. We found that Cr3+ significantly induced ECAK aggregation with a multi-phase kinetic process at a high dose of Cr3+. The spectrofluorimetric results showed that Cr3+-induced tertiary structural changes in ECAK caused extensive exposure of hydrophobic surfaces, which could be a triggering factor for inducing ECAK aggregation. Our study provides new information concerning the effect of Cr3+ on ECAK's enzymatic function and unfolding, including aggregation, which might be toxic or act as a negative regulator.