Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Dynamics of the nucleosome core particle revealed from a new database of high resolution x-ray crystallographic and simulated structures
The nucleosome core particle is a highly conserved structure which can play diverse roles depending on the organism, cell, or part of chromatin in which it resides. The Protein Data Bank currently contains approximately 70 nucleosome core particle structures, over half of which were determined in the last three years. The recent emergence of the field of epigenetics, and the increase in data available from experiments, warrants a need to develop new approaches to quantitatively compare various features of interest across multiple structures.
As a first step, we have developed a database and new computational tools to allow researchers to quantitatively analyze and compare the nucleosome core particle structures deposited in the Protein Data Bank. The features of the DNA-protein assembly can be examined in novel coordinate frames placed on the structure, allowing researchers to obtain a better understanding of the organization and subtleties of the macomolecular complexes. This comparison allows one to examine the 'motion' of any specific residue of interest, including sites of post-translational histone modification. The database also includes DNA-histone contact points, DNA conformational parameters, and information about protein features such as the secondary structure in the globular histone core and the 'motion' of the histone tails. Along with these features, we also characterize the dynamics of the global structure of the nucleosome core particle, including the changes in superhelical path of the DNA and the rearrangements of the histone tetramers. In addition to data obtained from crystallographically solved structures, we are working to incorporate data from in silico experiments. The data and the results of the analysis are available to the public as an automatically-updated, online-accessible web server.
Cartoon diagrams of crystal structures are shown with their reference frames aligned. The frames were computed by PCA of the globular core of the histone octamer. The anionic atoms of aspartic acid and glutamic acid are marked in light red. The cationic atoms of the arginines and lysines are marked in dark blue. Note the channels that the charges may occupy.