The RNA polymerase (gene product NS5B) from the hepatitis C virus is responsible for replication of the viral genome and is a validated drug target for new therapeutic agents. NS5B has a structure resembling an open right hand (containing the fingers, palm, and thumb subdomains), a hydrophobic C-terminal region, and two magnesium ions coordinated in the palm domain. Biochemical data suggest that the magnesium ions provide structural stability and are directly involved in catalysis, while the C-terminus plays a regulatory role in NS5B function. Nevertheless, the molecular mechanisms by which these two features regulate polymerase activity remain unclear. To answer this question, we performed molecular dynamics simulations of NS5B variants with different C-terminal lengths in the presence or absence of magnesium ions to determine the impact on enzyme properties. We observed that metal binding increases both the magnitude and the degree of correlated enzyme motions. In contrast, we observed that the C-terminus restricts enzyme dynamics. Under certain conditions, our simulations revealed a fully closed conformation of NS5B that may facilitate de novo initiation of RNA replication. This knowledge is important because it fosters the development of a comprehensive description of RNA replication by NS5B and is relevant to understanding the functional properties of a broad class of related RNA polymerases such as 3D-pol from poliovirus. Ultimately, this information may also be pertinent to designing novel NS5B therapeutics.