Three dimensional molecular modeling studies in AIDS research using high performance computing facilities: a ternary complex of HV-1 RT

The authors present here a complete three-dimensional molecular model structure of the ternary complex (Enzyme-DNA-dNTP) of human immunodeficiency virus-type 1 reverse transcriptase (HIV-1 RT) using high performance computer simulation and molecular modeling techniques. The Ca coordinates of the crystal structure of HIV-1 RT-DNA binary complex as well as biochemical properties of a number of mutant enzymes were used as the basis to model build a prepolymerase ternary complex in which Mg²⁺ ions are also accommodated. The side chains of amino acid residues interacting with the template and primer strands and those stabilizing the dNTP and Mg²⁺ ions in the active site pocket are clearly elucidated in the model. The structural information provided by this model should be useful in understanding the polymerase reaction mechanisms and should permit structure based drug design against HIV-1 RT