title: Dependence of DNA polymerase replication rate on external forces: a model based on molecular dynamics simulations.
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.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Ioan
authors.initials: I
authors.lastname: Andricioaei
authors.forename: Anita
authors.initials: A
authors.lastname: Goel
authors.forename: Dudley
authors.initials: D
authors.lastname: Herschbach
authors.forename: Martin
authors.initials: M
authors.lastname: Karplus
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry; D004256:DNA Polymerase I; D017931:DNA Primers / Q000737:chemistry; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D019277:Entropy; D006358:Hot Temperature; D008958:Models, Molecular; D015233:Models, Statistical; D008962:Models, Theoretical; D008968:Molecular Conformation; D009711:Nucleotides / Q000737:chemistry; D011487:Protein Conformation; D013696:Temperature; D013824:Thermus / Q000201:enzymology; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D017931:DNA Primers; D009711:Nucleotides; D014867:Water; D004247:DNA; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase