A multidisciplinary group has been assembled to undertake a cooperative effort devoted to the expression and purification of HIV proteins and the development of experimental and theoretical methods to study their structures. The expression, purification and scale-up efforts described in Program 1 will be concerned with the virally encoded HIV proteins, tat-III trans-activator, reverse transcriptase, the highly specific protease responsible for the cleavage of the Pr-gag and Pr-gag-pol proteins to their mature virion proteins, and Pr-gag, the substrate for the protease. In Program 2, theoretical methods will be undertaken to develop procedures for the design of inhibitors for a number of enzymes involving methods based upon fitting and matching topological features to active sites. Program 3 deals with the development of robotic control of procedures to study automated methods for crystallization of peptides and proteins and investigation of their structures, investigation of a trypsin-trypsin inhibitor complex by X-ray crystallography and theoretical studies on solvation energies and methods for predicting complementarity at protein interfaces. The efforts in Program 4 will be directed to the design of new NMR pulse sequences to facilitate the acquisition and the derivation of information on the structure and dynamics of proteins, including the HIV encoded proteins tat-III and the gag- pol protease. The efforts of Program 5 will be concerned with the development and application of new mass spectrometric methods to study HIV encoded coat glycoproteins, GP-160 and GP-120, and the T4 receptor. The proposed studies will be concerned with determining the structures of the oligosaccharide components and their functional significance in these glycoproteins.
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