write-up.doc - Bishop Theoretical Molecular Modeling Lab

An interdisciplinary team of scientist at Tulane and LSU has achieved high performance computing
across widely distributed supercomputing resources. This enabled us to conduct the first ever all atom
fully solvated molecular dynamics study of nucleosome positioning on a genome wide scale. To date we
have successfully distributed 1000’s of simulations across four supercomputing sites (NCSA, TACC, NICS,
LONI) and our own departmental resources. This enabled us to accumulate over 3µs (10Tb) of
molecular dynamics simulation of approximately 500 different realizations of the nucleosome.
Computationally: The tools we have developed for running many big jobs on widely distributed
supercomputing resources are not specific to any computation. Thus any supercomputer user with a
large number of computing tasks to perform can benefit from our workflow management tools. By
distributing simulations to whatever resources become available the time to completion of a
computational study is shortened AND the overall efficiency of shared supercomputing resources is
enhanced. A win-win situation that helps the individual researcher and the community of researchers
that shares the resources.
Biologically: This has enabled us to develop the first complete map of the structure and dynamics of
each of the sixteen different dinucleotide steps at each of the 146 positions in a nucleosome. This
information is critical to our understanding of the folding of DNA into nucleosomes and nucleosomes
into chromatin. Such packing occurs in all eukaryotic organisms and affects the biologic processes of
transcription, replication, regulation and repair.
Nucleosomes are a protein DNA complex in which 147 basepair of DNA are wrapped into a nearly two
turns of a superhelix. In humans, and other eukaryotes this folding of the DNA is necessary to pack it
into the cell nucleus because the length of a genome as a molecular fiber exceeds the width of the cell
nucleus. In case of humans this ratio is on the order of 1,000,000 to 1. The material properties of DNA,
(e.g. stiffness or flexibility) have a significant impact on the details of the packing, yet we do not
sufficiently understand the relationships. Simple physical models and sequence based rules have proven
insufficient to capture the biologic reality. All atom molecular dynamics simulations capture these
complexities but require a large number of simulations to extract and verify the generalities. In our case,
each simulation demands high performance computing resources (32 to 192 processors) running 2 to 12
hours at a time just to represent 1ns in the life of the 150,000 atoms of a solvated nucleosome.
RAJIB: I need to fill in titles etc… for this. You do too.
College of Engineering and Science, Louisiana Tech University, October 2010.
LaSIGMA, Tulane University (access grid: UNO, LaTech, LSU, Grambling, SUBR), November 2010.
Dept. Physics, Wesleyan University, Middletown, CT, November 2010.
Joint SE/SW Regional ACS Meeting, New Orleans, LA, December 2010.
*keynote speaker, 8th Annual Rocky Mtn. Bioinformatics Conf., Int’l Soc. Comp. Bio., Aspen, CO,
December, 2010.
RAJIB at LSU, LBRIN, ACS and Albany
Rajib Mukherjee, Shantenu Jha, Abhinav Thota, Hideki Fujioka, Thomas C. Bishop, “Running Many MD
Simulations on Many Super Computers” at 4th LBRN Computational Biology Workshop, March 18th and
19th 2011, Baton Rouge
T.C. Bishop and R. Mukherjee, “Nucleosomal DNA, kinked, not kinked or self-healing material” at Joint
SE/SW Regional ACS Meeting, New Orleans, LA, December 2010
Rajib Mukherjee, Thomas C Bishop, “Computational Study of Nucleosome Positioning and Stability” at
2011 Annual meeting of Biophysical Society, Baltimore.
Rajib Mukherjee, Hideki Fujioka, Abhinav Thota, Shantenu Jha, Thomas C. Bishop, “The Nucleosome
Simulator: 100 Nucleosomes; 2 Microseconds and Counting”, Albany 2011: The 17th Conversation
June 14-18 2011
Rajib will be a featured jr. scientist at Albany
Please fill in details on the manuscript w/ Shantenu and us
Rajib Mukherjee, Hideki Fujioka, Abhinav Thota, Thomas C. Bishop, Shantenu Jha, ““Running Many MD
Simulations on Many Supercomputers”, 2011 TeraGrid Conference, Association for Computing
Machinery (Submitted)
T.C. Bishop, Chromatin in 1, 2 and 3 dimensions: Comment on “Cracking the chromatin code: Precise
rule of nucleosome positioning” by E.N. Trifonov, Physics of Life Reviews, 2011.
T.C. Bishop and R. Mukherjee. Nucleosomal DNA, kinked, not kinked or self-healing material, to appear
in Frontiers in Nucleic Acids an ACS Symposium Series, edited by Richard D. Sheardy 2011.