MOLECULAR DYNAMICS SIMULATIONS OF SITE-SPECIFIC PROTEI-DNA INTERACTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We were awarded service units on the TCS in the form of a Medium Resource Allocation grant to address hypotheses regarding the role of dynamics in restriction endonuclease specificity. One of the aims of this grant was to use computational simulations to study the interactions of a promiscuous mutant EcoRI endonuclease with its DNA recognition site. We used molecular dynamics (MD) simulations to ask if simulations could reproduce the relatively subtle differences between mutant and wild-type complexes that were observed by x-ray crystallography. Indeed, the MD trajectories confirm many of the features observed in the experimental structures. The computational data also point to some novel differences between the two complexes that warrant further investigation by conducting simulations of significantly increased duration. When we applied for service units, we based the amount of our request on published benchmarks for a system with size similar to ours, running the pmemd code (Amber8 software suite) on the TCS. These benchmarks do not include the time required for file i/o which represents a significant barrier to efficient scaling when writing to disc volumes on the TCS. Thus our MRAC allocation will run out before we are able to address some of the interesting questions prompted by our simulations. We engaged in extended discussions with PSC scientists Troy Wymore and Shawn Brown who strongly recommended investigating the possibility that running simulations of our systems on the Cray XT3 will improve both scaling and throughput. We would therefore like to request a development allocation of service units on the XT3 as a means to extend the duration of our current simulations as well as to explore the capabilities of this new PSC resource to make more efficient use of future supercomputer time.