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

Ioan Andricioaei, Anita Goel, Dudley Herschbach, Martin Karplus

Journal: Biophysical journal 2005;87(3):1478-97

PMID: 15345530

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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.

Address: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

DOI: 10.1529/biophysj.103.039313

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MeSH Terms: Binding Sites, Computer Simulation, DNA, DNA Polymerase I, DNA Primers, DNA Replication, DNA-Directed DNA Polymerase, Entropy, Hot Temperature, Models, Molecular, Models, Statistical, Models, Theoretical, Molecular Conformation, Nucleotides, Protein Conformation, Temperature, Thermus, Time Factors, Water