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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Modeling and Informatics of DNA, Nucleosomes and Chromatin from Base Pairs to Genomes

Genomics is a sequence based informatics science and a structure based molecular science. Nucleosomes are the fundamental building blocks of chromatin, the biomaterial that houses the genome in all higher organisms. There are approximately 160 atomic resolution structures of the nucleosome available from the protein data bank. Collectively they explore histone mutations, species variations, binding of drugs and ionic effects but only a few sequences of DNA. Given a four-letter code (A, C, G, T) there are on the order of 4147 ~ 1088 possible sequences of DNA that can form a nucleosome. Exhaustive studies are not possible. Here we introduce G-Dash, a web based genome dashboard, specifically designed to integrate informatics and 3D material studies of DNA, nucleosomes and chromatin, and TMB-iBIOMES, a database containing over 20 microseconds of all atom molecular dynamics simulations representing over 500 different realizations of the nucleosome. G-Dash unites Interactive Chromatin Modeling (ICM), the Biodalliance genome browser and the JSmol molecular viewer to fold any DNA sequence into atomic or coarse-grained models of DNA, nucleosomes or chromatin. The exchange of data between informatics and structure is bi-directional so any informatics track can inform a molecular structure (e.g. fold by MNase activity) and structure features can be displayed as informatics tracks in a genome browser (e.g. Roll, Slide, or Twist). Our TMB-iBIOMES database serves as a reference for comparative, on-demand simulations of nucleosomes. Every simulation deposited in TMB-iBIOMES contains Amber formatted topology and coordinate input files, NAMD formatted output, log and trajectory files, and RMSD and DNA helical parameter data. Closely related simulations in TMB-iBIOMES are grouped together and a summary analysis is provided. All data can be navigated in a file browser or iBIOMES-Lite web browser format or downloaded with command line tools. It demonstrates that the workflow and simulation protocols developed are robust, that DNA sequence can affect the structure and dynamics of nucleosomal DNA at some locations but not others, and that sequence effects on nucleosome structure and dynamics can be observed in 10’s of nanoseconds. TMB-iBIOMES and G-Dash work together to provide a novel means for investigating structure-function relationships for regions of the genome ranging from base pairs to chromosomes.

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Figure 1. Left: TMB-iBIOMES is an iBIOMES-lite database with over 20ms of trajectory and analysis data for over 500 unique realizations of the nucleosome; Middle: A collection of Molecular Views representing the interactive capabilities of G-Dash; Right: G-dash integrates the informatics capabilities of a Genome Browser (top) with atomic and coarse-grained compute engines via a Control Panel (bottom).

This effort was supported by NIH IDEA grants 5 P20 GM103424-15 and 3 P20 GM103424-15S1 and the NSF OIA-1541079 and the Louisiana Board of Regents.

References

    TMB-iBIOMES is available at http://dna.engr.latech.edu/~ibiomes/

    G-Dash is available at http://dna.engr.latech.edu/~gdash/

Ran Sun
Zilong Li
Thomas C. Bishop

College of Engineering and Science
Louisiana Tech University
Ruston, LA 71272

Ph: (318) 257-5209
Fax: (318) 257-4000
e-mail: bishop@latech.edu