INTERACTIONS BETWEEN HUMAN SLINGSHOT PHOSPHATASE 2 AND PHOSPHO-COFILIN: A MOLECULAR DYNAMICS STUDY

Abstract

Human slingshot phosphatase 2 (SSH2) is one of the dual specificity protein tyrosine phosphatases, which can activate cofilin substrate by binding its phosphorylation state. Because the interaction model of SSH2 and phospho-cofilin (P-cofilin) was unknown, we obtained the complex through macromolecular docking method. The molecular dynamics studies were used to investigate the complex dynamics in an aqueous solution. To understand the binding specificity, the free energy was calculated with the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) approach and the interaction mode in active site was analyzed. The results indicated that the interaction of the P-loop of SSH2 with phosphoserine of human P-cofilin was stabilized by molecular mechanics energy and nonpolar solvation energy components, while polar solvation energy and the entropic contributions were unfavorable for the combination of the two proteins. In addition, the electrostatic contributions were negative for the formation of the complex on the whole, but seen from the active local, the Coulomb interaction between the phosphoserine and the P-loop residues could play an important role in determining substrate specificity.