Journal:JBSD:17

DNA Conformation and Energy in Nucleosome Core: A Theoretical Approach

Davood Norouzi and Farshid Mohammad-Rafiee ^[1]

Molecular Tour
DNA in eukaryotes is packaged into nucleosomes by wrapping around positively charged histone proteins. Each histone octamer is associated with 147 base pairs (bps) of DNA, in which the DNA is wrapped in about 1.65 turns around the core particle of histone proteins. The complex of DNA and histone proteins is ubiquitous in eukaryotic nuclei and has a major role in many essential life processes. Recent experiments revealed a lot of information about the structure and positioning of nucleosomes along the genome.

DNA conformation in complex with proteins is far from its canonical B-form. The affinity of complex formation and structure of DNA depend on its attachment configuration and sequence. In this article, we develop a mechanical model to address the problem of DNA structure and energy under deformation. The structure and energy of nucleosomal DNA is calculated based on its sequence and positioning state. The inferred structure has remarkable similarity with X-ray data. NCP147 sequence based on PDB data is in yellow, (PDB entry 1kx5) and our inferred structure is in red; click here to see this from the side view, you can see also animation of this superposition. The superposition of small fragments of DNA structure from PDB data (yellow) and our predicted structure (red) shows a smooth bending toward the major groove in dyad axis area at sequence TGGAATCCA. The two structures demonstrate very good similarity when deformations in DNA bases are smooth (click here to see animation).

Comparison of small fragments of DNA structure from PDB data (yellow) and our predicted structure (red) at sequence TTGGAAACT shows that there are two considerable kinks and a large slide in the crystal structure while the inferred structure shows a smooth bending. The linear model cannot predict these nonlinearities, but position of large kinks and slide are predicted by the model with lower range of values (click here to see animation). Although there is no sequence-specific interaction of bases and the histone core, we found considerable sequence dependency for the nucleosomal DNA positioning. We argue that structural energy determines the natural state of nucleosomal DNA and is the main reason for affinity differences in vitro. This theory can be utilized for the DNA structure and energy determination in protein-DNA complexes in general.