Structural flexibility of the nucleosome core particle at atomic resolution studied by molecular dynamics simulation

Area of Science:

• Structural biology
• Molecular dynamics simulations
• Biophysics

Background:

• Nucleosome core particles are fundamental units of DNA packaging in eukaryotes.
• Histone N-terminal tails are intrinsically disordered and play crucial roles in gene regulation.
• Understanding the dynamics of histone tails and their interaction with DNA is key to deciphering epigenetic mechanisms.

Purpose of the Study:

• To investigate the dynamics of histone N-terminal tails in a complete nucleosome core particle.
• To study how DNA bending and nucleosome packing influence DNA structure and dynamics.
• To analyze the mobility of DNA segments within the nucleosome.

Main Methods:

• Comparative explicit solvent molecular dynamics (MD) simulations.
• Simulations performed on a nucleosome core particle with and without N-terminal histone tails (>20 ns).
• Analysis of conformational changes, DNA backbone conformations, kinks, bends, and superhelical mobility.

Main Results:

• Histone and DNA structures remained stable, validating the force field approach.
• No significant increase in noncanonical DNA backbone conformations was observed despite packing strain.
• Histone N-terminal tails underwent rapid conformational rearrangements, associating with DNA grooves and modulating DNA accessibility.

Conclusions:

• Histone N-terminal tails exhibit significant dynamics, rapidly interacting with DNA.
• Nucleosome packing and DNA bending do not induce major DNA backbone alterations.
• The dynamic interactions of histone tails can modulate DNA accessibility on the nanosecond timescale.