Dependence of DNA polymerase replication rate on external forces: a model based on molecular dynamics simulations |
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Authors: | Andricioaei Ioan Goel Anita Herschbach Dudley Karplus Martin |
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Institution: | Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. |
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Abstract: | Molecular 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 determined 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 experiment. Simulations above 40 pN reveal large conformational changes in the enzyme-bound DNA that may have a role in the force-induced exonucleolysis observed experimentally. |
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