Abstract:
:We propose a model for DNA polymerase fidelity in which free energy differences, delta delta G, between matched and mismatched nucleotides are magnified at the enzyme's active site. Both hydrogen bonding and stacking components of the interaction energy are amplified, with the most profound effect being on the magnitude of hydrogen-bonding interactions. Magnification in delta delta G values follows from the exclusion of water around base pairs in the active site cleft of the enzyme. After showing that base-pair dissociation energies calculated from hydrogen-bonding and base-stacking interactions in vacuo are greatly reduced by water, it is proposed that water removal results in a proportional restoration of these contributions to base pairing. Assuming approximately equal to 40% exclusion of surrounding water, one predicts magnified values of delta delta G sufficient to account for polymerase insertion and proofreading fidelity, thereby avoiding the need to postulate additional active site constraints in order to select or reject nucleotides.
journal_name
Proc Natl Acad Sci U S Aauthors
Petruska J,Sowers LC,Goodman MFdoi
10.1073/pnas.83.6.1559subject
Has Abstractpub_date
1986-03-01 00:00:00pages
1559-62issue
6eissn
0027-8424issn
1091-6490journal_volume
83pub_type
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