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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Andricioaei I,Goel A,Herschbach D,Karplus M

doi

10.1529/biophysj.103.039313

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

1478-97

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(04)73632-2

journal_volume

87

pub_type

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