Project abstract for group harrschu

Particle Mesh Ewald (PME) Periodic Boundary Dynamics

These researchers are conducting experiments investigating the mechanism(s) of a genetic switch controlled by DNA regulatory proteins. They are interested in steroid hormone receptor protein interactions with DNA in the pathogenesis of breast cancer. The researchers have previously reported on a mechanism describing how these DNA regulatory proteins recognize and bind to their specific sites on DNA. They are conducting Particle Mesh Ewald (PME) periodic boundary molecular dynamics simulations in solvent to investigate hydrogen bonding, van der Waals, and long-range electrostatic interactions between amino acids of the DNA regulatory proteins and nucleotides of their cognate DNA binding sites. They are now using the NAMD program, which is a parallel, object-oriented molecular dynamics code designed for high-performance simulation of large biomolecular systems. They are currently conducting NAMD simulations on a nucleosome model of the 5’ long terminal repeat nucleotide sequence upstream of the mouse mammary tumor virus genome that contains well-characterized DNA binding sites glucocorticoid response elements (GREs) for steroid hormone receptor proteins in complex with the glucocorticoid receptor (GR) DNA binding domain (DBD).

The researchers are also computing PME periodic boundary solvated dynamic simulations on several other steroid receptor/DNA complexes. These studies include DNA containing various hormone response elements (cognate and non-cognate) in complex with members of the steroid receptor superfamily of proteins, particularly the estrogen, glucocorticoid, retinoic acid, and progesterone receptors.