Dependence of DNA polymerase replication rate on external forces: A model based on molecular dynamics simulations

Mol. dynamics simulations are presented for a Thermus aquaticus (Taq) DNA polymerase I complex (consisting of the protein, the primer-template DNA strands, and the incoming nucleotide) subjected to external forces.  The results obtained with a force applied to the DNA template strand provide insights into the effect of the tension on the activity of the enzyme.  At forces below 30 pN a local model based on the parameters detd. from the simulations, including the restricted motion of the DNA bases at the active site, yields a replication rate dependence on force in agreement with expt.  Simulations above 40 pN reveal large conformational changes in the enzyme-bound DNA that may have a role in the force-induced exonucleolysis obsd. exptl.