Paper Citing NAMD - Abstract
Mukherjee, Rajib; Bishop, Thomas C.
Nucleosomal DNA: Kinked, Not Kinked, or Self-Healing Material?
FRONTIERS IN NUCLEIC ACIDS, 1082:69-92, 2011
We use all atom molecular dynamics simulations to investigate the structure and dynamics of nucleosomal DNA. Our primary focus is characterization of DNA kinking as a function of position and base pair type within the nucleosome. For this purpose we have constructed 16 fully solvated all atom models of the nucleosome and subjected each to molecular dynamics simulations. Each system consists of over 200,000 atoms and is simulated for 16 ns. Combined the systems represent over 3.2 million atoms and 256 ns of nucleosome dynamics. Each system has a different sequence of DNA. The sequences chosen allow us to investigate each base pair type at each of the 147 positions in the nucleosome, as well as, each of the 16 dinucleotide steps at each of the 146 positions in the nucleosome. Within the limits of this approach we demonstrate that threading different DNA sequences onto a given histone core allows for successful initiation of molecular modeling. We also show that location within the nucleosome affects the structure and dynamics of a given base pair step type, i.e. the histones alter the DNA. However this effect is not so strong as to impose the same structure and dynamics on DNA regardless of sequence. Analysis of interaction energies demonstrates that the histone-DNA interactions vary more as a function of position than as a function of sequence. Moreover, the relative contribution from van der Waals interactions and from Coulomb interactions to the total histone-DNA interaction energy also varies with position. Thus the magnitude and the nature of the histone-DNA interactions vary with location. To analyze DNA kinking in the nucleosome we employed three definitions of kinks, included are a weak and a strong kink criteria. No single kink, by any definition, persisted for an entire 16 ns simulation. The longest continuous lifetime for an individual kink was approximately 6 ns. However, picosecond lifetimes are more typical. On nanosecond time scales kinks are self-healing, repeatedly appearing and disappearing at some locations. Kinking is not determined only by location or only by DNA sequence. Rather kinking results from a combination of the stresses imposed on DNA by the histone core and the sequence specific material properties of DNA. Both are decidedly non-uniform.
