Catalytic Magnesium as a Door Stop for DNA Sliding.

The protein HIV Reverse Transcriptase (HIV RT) synthesizes a DNA strand according to a template. During the synthesis, the polymerase slides on the double stranded DNA to allow the entry of a new nucleotide to the active site. We use Molecular Dynamics simulations to estimate the free energy profile and the time scale of the DNA-protein's relative displacement in the complex's closed state. We illustrate that the presence of the catalytic magnesium slows down the process. Upon removing the catalytic magnesium ion, the process is rapid and significantly faster than reopening the active site in preparation for the new substrate. We speculate that magnesium regulates DNA translocation. The magnesium locks the DNA into a specific orientation during the chemical addition of the nucleotide. The release of Mg2+ eases DNA sliding and the acceptance of a new substrate.