Unveiling Nucleosome Dynamics: A Comparative Study Using All-Atom and Coarse-Grained Simulations Enhanced by...

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Nucleosomes are fundamental units of DNA packaging in eukaryotes.
• Understanding nucleosome dynamics is crucial for gene regulation and DNA processes.
• Molecular dynamics simulations offer insights into molecular behavior at atomic and coarse-grained levels.

Purpose of the Study:

• To investigate nucleosome dynamics using all-atom and coarse-grained (CG) molecular dynamics simulations.
• To evaluate the performance of the SIRAH force field for nucleosome simulations.
• To compare the conformational sampling and DNA breathing motions between atomistic and CG models.

Main Methods:

• All-atom and coarse-grained (CG) molecular dynamics simulations.
• Simulation of two nucleosomal DNA sequences (ASP and Widom-601) for six microseconds.
• Comparative analysis of structural parameters (groove widths, base pair geometries).
• Principal component analysis (PCA) of DNA structural parameters.

Main Results:

• Good agreement in structural parameters between atomistic and CG models.
• CG simulations exhibited broader conformational sampling and increased DNA end breathing motion.
• PCA revealed multiple free energy minima, particularly in CG simulations.
• Sequence-dependent DNA behavior and repositioning were observed.

Conclusions:

• The SIRAH CG force field shows potential for studying large-scale nucleosome dynamics.
• CG simulations provide valuable insights into nucleosome conformational flexibility.
• Findings contribute to understanding sequence-specific DNA interactions within nucleosomes.