MOLECULAR DYNAMICS SIMULATIONS OF BUFORIN II TRANSLOCATION

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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. Antimicrobial peptides represent a potential alternative to conventional antibiotics, particularly against bacteria that have developed drug resistance. One intriguing peptide is buforin II (BF2), which is thought to kill bacteria by crossing the cell membrane and binding nucleic acids inside the cell. Ongoing research in our lab is investigating the BF2 membrane translocation mechanism on the molecular level using a variety of experimental techniques along with molecular dynamics (MD) simulations. Previously, we have primarily focused on simulations of a single BF2 peptide interacting with an explicitly represented lipid membrane, and these simulations provided useful insights into BF2lipid interactions. However, single peptide simulations do not allow us to consider potential cooperativity between peptides in translocation, such as the hypothesized formation of toroidal pores. Thus, are currently considering simulations of multiple BF2 peptides interacting with explicit lipid membranes, similar to recently published simulations of magainin and Tat peptides. We are requesting a developmental allocation to explore the use of TeraGrid for these larger systems that require more extensive computational resources. These simulations will utilize the GROMACS MD code that we employed for previous BF2 simulations. We plan to use our experience from this initial allocation to develop a more extensive TeraGrid proposal considering several BF2 mutations that we are also characterizing experimentally. Together, this computational and experimental data will help elucidate the structure-function relationships of BF2 translocation. An improved understanding of BF2 function will promote the design and application of novel antimicrobial and cell-penetrating peptides.