Molecular dynamics simulation-based investigation of LexA-DNA interaction: affinity-dependent conformational changes and implications for DNA looping

ContextThe binding of proteins to the DNA plays a crucial role in various cellular processes including gene expression. LexA is a bacterial transcription factor that binds to a specific DNA motif, leading to the regulation of numerous genes involved in the DNA damage response. Understanding the structural dynamics and mechanisms of DNA binding by LexA can provide valuable insights into its function and regulatory capabilities. Here, molecular dynamics (MD) simulations are used to investigate how the sequence of the DNA binding motif influences the conformational changes and bending behavior of DNA upon LexA binding. Simulation trajectories reveal that the DNA fragment containing a higher affinity LexA binding motif exhibits more pronounced bending and structural deformations compared to that containing a lower affinity binding motif. Additionally, bending of the protein itself is also observed in the presence of the DNA fragment with the higher affinity LexA binding motif. Our results confirm previous reports of LexA-induced DNA bending and shed further light on the structural details of the DNA bending mechanisms. MethodsMD simulations are employed to investigate the interaction between LexA and 70 bp-long DNA fragments that differ in the LexA binding motif. The GROMACS simulation package with the AMBER14SB force field for proteins and the AMBERparmbsc1 force field for nucleic acids is used to conduct 100 ns-long all-atom simulations. The solvent is set up with the TIP3P water model and the simulation box is filled with ions to reach 0.15 M salt concentration.