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| About Rommie Amaro (UCSD) |
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Rommie Amaro is a native of the south side of Chicago and earned her bachelor’s degree in Chemical Engineering with high distinction from the University of Illinois at Urbana- Champaign (UIUC) in 1999. After graduating, she joined Kraft Foods, Inc. as an Associate Research Engineer in Glenview, Illinois, working mainly on Philadelphia Cream Cheese productivity and commercialization projects. After two years of working with condensed matter, she returned to UIUC to attend graduate school in Chemistry.
She earned her Ph.D. in Chemistry in the lab of Zan Luthey-Schulten, where she worked mainly on computational methods to reconstruct free energy profiles from non-equilibrium pulling experiments of ammonia conduction through a beta barrel protein involved in histidine biosynthesis and studying mechanisms of allosteric regulation in proteins. While a graduate student, she also worked closely with the NIH Resource for Macromolecular Modeling and Bioinformatics, where she helped develop a series of workshops that have now been taught on three separate continents.
Rommie is presently a postdoc in the lab of J. Andrew McCammon at the University of California, San Diego and a NIH Kirschstein-NRSA postdoctoral fellowship recipient working on new methods to incorporate receptor flexibility in computer-aided drug design, working mainly on targets involved in infectious diseases. She is an alternate councilor for the American Chemical Society’s Division of Computers in Chemistry, President of the Tau Chapter of Graduate Women in Science, and will be joining the faculty of the University of California, Irvine in 2009.
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Comparative Studies using Explicit and Generalized Born Molecular Dynamics Simulations of Influenza Neuraminidases
Rommie E. Amaro, University of California, San Diego
Avian influenza virus type A, subtype H5N1, is becoming the world’s largest pandemic threat due to its high virulence and lethality in birds, quickly expanding host reservoir, and high rate of mutations. Antigenic drift has given rise to new strains that are resistant to existing drugs and antigenic shift is resulting in new virulent subtypes of the flu virus, underscoring the need to design novel therapeutics. The first crystal structures of a group-1 NA in apo form and in complex with currently available drugs revealed that although the binding pose of Tamiflu was similar to that seen in previous crystallographic complexes, the 150-loop adopted a distinct conformation, opening a new cavity adjacent to the active site. These structures also suggested a slow conformational change may occur upon inhibitor binding. Despite this detailed structural information, the interpretation of the loop dynamics based on crystal structures alone is a difficult task. As a complement to the crystallographic structures, all-atom explicit solvent and generalized Born molecular dynamics (MD) simulations of the apo and Tamiflu-bound systems were carried out. These extensive simulations suggested that the 150-loop and adjacent binding site loops may be even more flexible than observed in the crystal structures. In addition, comparison of the avian- and human-type NAs are carried out. The comparative dynamics of the NAs that we present here allow us to make insights into the flexibility of the 150- and 430-loops, which are important due to their proximity to the sialic-acid binding site. Furthermore, the dynamics of residues that have been shown by computational solvent mapping and ligand docking to be potentially important in the binding of ligands to this expanded area are investigated and discussed. Lastly, the relative positions of Tamiflu in the different systems are reported and interpreted in the context of developing more specific inhibitors against the N1 strain.
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