DNA replication is a fundamental processes in cell cycle, where parent DNA reproduces two identical copies of itself. This process requires the synchronized function of more than 30 proteins, involving many protein-protein and protein-DNA interactions keeping the replisome in a working condition. New generations of antibiotics could disrupt these interactions, halting DNA replication in bacterial pathogens.

Single stranded DNA-binding protein (SSB) is a two domain protein essential to DNA replication.  It is comprised of an oligonucleotide/oligosaccharide binding (OB) domain that binds to ssDNA (protecting it from damage during replication), and a disordered C-terminal domain. SSB interacts with more than 14 proteins involved in different stages of DNA replication, repair, replication restart and recombination. This occurs through a highly conserved 6-residue motif at the C-terminus (SSB-Ct, DDDIPF-COOH) (Shereda, Kozlov et al. 2008). The structure, function and behavior of SSB-Ct in complex with its binding partners is of interest. Currently, four crystal structures are available of SSB-Ct in complex with its binding partners: RecO (Ryzhikov, Koroleva et al. 2011), ExoI (Lu and Keck 2008), the PolIII cj complex (Marceau, Bahng et al. 2011), and DnaG (primase) C-terminal domain (Tak Lo, A. Oakley, unpublished). While the six residues of SSB-Ct are important for binding, only the last 3-5 residues of SSB-Ct peptide have been observed in an electron density maps.  

Molecular dynamic (MD) simulation is a powerful theoretical method that may give insight into protein motion at an atomic level. A set of 100 ns molecular dynamic simulations of SSB-Ct interacting with with the above proteins have been calculated in order to further understand the interactions between SSB-Ct and its binding partners, identify key features of this protein-protein interaction, similarities in binding modes, and to examine conformational changes and electrostatic of interactions. Furthermore, the impact of SSB-Ct mutations have been assessed. All MD simulations were carried out using NAMD software (Phillips, Braun et al. 2005).