BioPhysics & Condensed Matter Seminar: Dr. Aykut Erbas, Northwestern University  Add To Calendar

  • Date(s): Thursday, 4/5 3:30 PM to Thursday, 4/5 4:30 PM
  • Speaker: Dr. Aykut Erbas
  • Host: Prof. Ursula Perez-Salas
  • Campus Address: 2214 SES
Title: Unbinding and Binding Kinetics of Molecular Ligands

Abstract: Unbinding and binding kinetics of molecular ligands, such as DNA-binding proteins, to specific or nonspecific binding sites, control many biological processes in living cells from regulatory networks to cell signaling but also a key factor for designing efficient drugs. One set of proteins that can control the critical processes by binding and unbinding to DNA are transcription factors (TFs). According to the standard picture of biomolecular interactions, the dwelling time of TFs on DNA molecules in cells is independent of their concentration in solution. However, recent studies challenge the standard picture by demonstrating cases, where unbound proteins in solution indeed accelerate TF dissociation rates. Using single-molecule experiments, molecular dynamics simulations and analytical approaches, we measured and analyzed dissociation kinetics of Fis (factor for inversion stimulator) from single-DNA binding sites. We found a strong concentration dependence, which can be explained by a facilitated dissociation (FD) mechanism induced by unbound proteins in solution. Furthermore, while unbinding is regulated by electrostatic and local non-electrostatic interactions between ligands and binding sites, our simulations and scaling analysis revealed that rebinding is mainly controlled by the distribution of binding sites and length scales of the interaction volume through which ligands can diffuse.  Our results suggest both FD-assisted unbinding and diffusion-controlled rebinding could have a profound effect on the dynamics of biological processes that depend on the binding of molecular ligands in vivo.

Cm-Bio 4-5 Erbas flyer