An abridged transition state model to derive structure, dynamics, and energy components of DNA polymerase β fidelity.

ABSTRACT: We show how a restricted reaction surface can be used to facilitate the calculation of biologically important contributions of active site geometries and dynamics to DNA polymerase fidelity. Our analysis, using human DNA polymerase beta (pol β), is performed within the framework of an electrostatic linear free energy response (EFER) model. The structure, dynamics, and energetics of pol β-DNA-dNTP interactions are computed between two points on the multidimensional reaction free energy surface. "Point 1" represents a ground state activation intermediate (GSA), which is obtained by deprotonating the terminal 3'OH group of the primer DNA strand. "Point 2" is the transition state (PTS) for the attack of the 3'O(-) (O(nuc)) on the P(α) atom of dNTP substrate, having the electron density of a di

SUBMITTER: Klvana M 

PROVIDER: S-EPMC3477174 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature