In this year we devoted extensive effort to the development of improved force fields that can interface seamlessly with quantum chemical methods, in particular Density Functional Theory, to study the reaction mechanisms HIV-1 macromolecules. Due to the high concentration of charged amino acid and nucleic acid residues, as well as the presence of metal ions, the treatment of short ranged and long ranged electrostatics is critical to achieving reliable results. We have also initiated an effort to develop an all-atom model for the HIV-1 Integrase system, for which an x-ray crystal structure became available within the past year.

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Cisneros, G Andrés; Perera, Lalith; Schaaper, Roel M et al. (2009) Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights into active site metal coordination and catalytically significant residues. J Am Chem Soc 131:1550-6
Li, Wenxue; Huang, Yan; Reid, Rollie et al. (2008) NMDA receptor activation by HIV-Tat protein is clade dependent. J Neurosci 28:12190-8
Cisneros, G Andres; Perera, Lalith; Garcia-Diaz, Miguel et al. (2008) Catalytic mechanism of human DNA polymerase lambda with Mg(2+) and Mn(2+) from ab initio quantum mechanical/molecular mechanical studies. DNA Repair (Amst) 7:1824-34