Communications: Electron polarization critically stabilizes the Mg ²⁺ complex in the catalytic core domain of HIV-1 integrase

In this paper, we present a detailed dynamics study of the catalytic core domain (CCD) of HIV-1 integrase using both polarized and nonpolarized force fields. The numerical results reveal the critical role of protein polarization in stabilizing Mg²⁺ coordination complex in CCD. Specifically, when nonpolarized force field is used, a remarkable drift of the Mg²⁺ complex away from its equilibrium position is observed, which causes the binding site blocked by the Mg²⁺ complex. In contrast, when polarized force field is employed in MD simulation, HIV-1 integrase CCD structure is stabilized and both the position of the Mg²⁺ complex and the binding site are well preserved. The detailed analysis shows the transition of α-helix to 3₁₀-helix adjacent to the catalytic loop (residues 139-147), which correlates with the dislocation of the Mg²⁺ complex. The current study demonstrates the importance of electronic polarization of protein in stabilizing the metal complex in the catalytic core domain of HIV-1 integrase.