Molecular dynamics simulations of papilloma virus E2 DNA sequences: dynamical models for oligonucleotide structures...

Area of Science:

• Molecular Biology
• Structural Biology
• Biophysics

Background:

• The papilloma virus E2 protein's DNA binding specificity is a key example of indirect readout, where DNA sequence elements not in direct contact influence binding.
• Understanding this interaction is crucial for deciphering structural codes in DNA recognition by regulatory proteins.

Purpose of the Study:

• To characterize the solution structure of the E2 DNA sequence d(ACCGAATTCGGT) using molecular dynamics (MD) simulations.
• To investigate the dynamic structural changes of E2 DNA upon protein binding and the stability of the protein-bound conformation in solution.

Main Methods:

• Conducted multiple MD simulations of the E2 DNA oligonucleotide d(ACCGAATTCGGT) in solution, including counterions and water.
• Utilized canonical and crystallographic structures as starting points for simulations.
• Performed MD simulations on a longer E2 DNA sequence (16-mer) in its protein-bound conformation.

Main Results:

• MD simulations converged to a single dynamical structure for d(ACCGAATTCGGT) in solution, consistent with two of three crystal structures.
• A significant DNA helix kink observed in one crystal structure may be a packing artifact.
• The protein-bound DNA structure is dynamically unstable in the absence of the E2 protein, indicating sequence-intrinsic and protein-induced contributions to binding.

Conclusions:

• The solution structure of E2 DNA is primarily determined by its sequence, with specific steps influencing curvature.
• The protein-bound DNA conformation is stabilized by the E2 protein, highlighting the dynamic nature of protein-DNA recognition.