DNA sliding clamps are toroid-shaped proteins that encircle DNA and slide along the DNA backbone. They play a crucial role serving as a scaffold for enzymes that act on DNA, specifically during replication by tethering DNA polymerase to the growing strand, increasing the processivity. The ring-shaped protein is able to diffuse along the DNA in a random walk, however the molecular nature of this process is poorly understood.<br/>Whether sliding clamp diffusion along DNA is governed by simple Brownian motion or driven by internal motions of the DNA remains an elusive question. Here we investigate the DNA motion-driven diffusion hypothesis. We have employed molecular dynamics to sample the movement of sliding clamps in complex with a 30mer DNA duplex. Each sampled clamp presents a unique inner pore diameter and electrostatic environment, which is thought to influence the propagation. A smaller pore diameter presumably results in more protein-DNA contacts and may result in less DNA flexibility.  If DNA motions contribute to sliding clamp diffusion, more rigid DNA would likely result in slower diffusion, restricting the speed at which a protein with a smaller pore diffuses. To further understand the driving force behind sliding clamp diffusion, we have quantified the protein-DNA interactions for each clamp. Additionally, we have analyzed the global motions of the protein by constructing a Markov state model that describe kinetics of the clamp diffusion. By combining the description of the protein-DNA interactions with a kinetic model of the diffusion, new insight into the sliding clamp diffusional processes has been gained.

Molecular basis of sliding clamp diffusion along DNA

251st National Meeting (2016)

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