Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein–DNA Complexes

نویسندگان

  • Chuanying Chen
  • Alexandre Esadze
  • Levani Zandarashvili
  • Dan Nguyen
  • B. Montgomery Pettitt
  • Junji Iwahara
چکیده

Intermolecular ion pairs (salt bridges) are crucial for protein-DNA association. For two protein-DNA complexes, we demonstrate that the ion pairs of protein side-chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP-SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015