This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Trinucleotide repeat sequences are now linked to several genetic diseases such as fragile X syndrome, myotonic dystrophy, and Huntington disease. It seems that these sequences create stronger binding with core-histones than random DNA sequences therefore repressing transcription. It is not exactly clear from experiments if this tight binding is due to an increase in DNA flexibility over these aforementioned sequences. We have recently developed a protocol to investigate the mechanical properties of DNA by coupling elastic rod theory and all-atom methods efficiently implemented with the use of analytical second derivatives in an implicit solvent environment (using either the MPI or OpenMP protocol). Additionally, the effects of salt concentration on these sequences and their binding to core-histone proteins is another interesting problem that we would like to study in more details . These problems require challenging all-atom calculations including at least 25 000 atoms; calculations of this magnitude have rarely if ever been carried out. These calculations require at least 70 GB of memory and 16CPU's, a large shared memory computer is therefore well suited for this problem. References: Brown, RA, Author Brown Russell A. Brown, Russell A. , Case, DA, et al. Second derivatives in generalized born theory J COMPUT CHEM 27 (14): 1662-1675 (2006) T. Macke and D.A. Case. Modeling unusual nucleic acid structures. Molecular Modeling of Nucleic Acids, N.B. Leontes and J. SantaLucia, Jr., eds. (Washington, DC: American Chemical Society, 1998), pp. 379-393. Albino Bacolla, Robert Gellibolian, Miho Shimizu, Sorour Amirhaeri Seongman Kang, Keiichi Ohshima, Jacquelynn E. Larson, Stephen C. Harvey B. David Stollar, and Robert D. Wells Flexible DNA: Genetically Unstable CTGCAG and CGGCCG from Human Hereditary Neuromuscular Disease Genes J. Bio. Chem. 272 (27): 1678316792 (1997 ) James S. Godde and Alan P. Wolffe Nucleosome Assembly on CTG Triplet Repeats J. Bio. Chem. 271, (25), 1522215229 (1996)
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