DNA Polymerase III of <i>E. coli</i> is a multi-subunit enzyme that efficiently catalyzes the replication of DNA. Four of the subunits termed Pol III* include the polymerase (α)  and exonuclease (ε) domain, the clamp (β) and an accessory protein (θ). Previous work has shown that a variety of mutations, specifically L82E and L82D, within the monomers of the β-clamp lead to destabilization. We have shown via molecular dynamic simulations that these distal mutations can have effects across the entire polymerase, particularly within the ε subunit. To gain further insight into how the reaction within ε is affected, we utilized quantum mechanics/molecular mechanic calculations on the exonuclease reaction. These calculations aim to shed light on how the proofreading activity of DNA Pol III* may be affected with these mutations.

Insights via QM/MM into the effects of distal mutations on the exonuclease activity of DNA polymerase III*

ACS Spring 2022

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