Searching for Low Probability Opening Events in a DNA Sliding Clamp

Abstract

The β subunit of E. coli DNA polymererase III is a DNA sliding clamp associated with increasing the processivity of DNA synthesis. In its free form, it is a circular homodimer structure that can accomodate double-stranded DNA in a nonspecific manner. An open state of the clamp must be accessible before loading the DNA. The opening mechanism is still a matter of debate, as is the effect of bound DNA on opening/closing kinetics. We use a combination of atomistic, coarse-grained, and enhanced sampling strategies in both explicit and implicit solvents to identify opening events in the sliding clamp. Such simulations of large nucleic acid and their complexes are becoming available and are being driven by improvements in force fields and the creation of faster computers. Different models support alternative opening mechanisms, either through an in-plane or out-of-plane opening event. We further note some of the current limitations, despite advances, in modeling these highly charged systems with implicit solvent.