Comparison of nucleotide interactions in water, proteins, and vacuum: model for DNA polymerase fidelity.

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.

authors

Petruska J,Sowers LC,Goodman MF

doi

10.1073/pnas.83.6.1559

subject

Has Abstract

pub_date

1986-03-01 00:00:00

pages

1559-62

issue

6

eissn

0027-8424

issn

1091-6490

journal_volume

83

pub_type

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