title: Communications: Electron polarization critically stabilizes the Mg2+ complex in the catalytic core domain of HIV-1 integrase.
abstract: 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 Mg(2+) coordination complex in CCD. Specifically, when nonpolarized force field is used, a remarkable drift of the Mg(2+) complex away from its equilibrium position is observed, which causes the binding site blocked by the Mg(2+) 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 Mg(2+) complex and the binding site are well preserved. The detailed analysis shows the transition of alpha-helix to 3(10)-helix adjacent to the catalytic loop (residues 139-147), which correlates with the dislocation of the Mg(2+) 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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Lu
authors.forename: Ye
authors.initials: Y
authors.lastname: Mei
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D020134:Catalytic Domain; D004583:Electrons; D004795:Enzyme Stability; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation
chemical_list: D019427:HIV Integrase; D008274:Magnesium; C514801:p31 integrase protein, Human immunodeficiency virus 1