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FOLDING THE SHEETS: USING COMPUTATIONAL METHODS TO PREDICT THE STRUCTURE OF PROTEINS 254 are necessary to improve our understanding of catalysis. Honig and coworkers have used the Poisson-Boltzmann equation to obtain a better understanding of protein electrostatics (Gilson and Honig, 1986). Distinct dielectric environments can be accommodated, and while closed-form solutions are not possible for any complex systems, finite difference methods can be used to calculate the field strength. These studies have proved useful in replicating pKa data, and efforts are under way to incorporate the Poisson-Boltzmann formalism into existing potential functions. Unfortunately, these calculations are computationally intensive. Little has been tried to exploit electrostatic interactions as a guide to the merits of a protein structural model. Finally, experimental information can be used to sort correct from incorrect structures. The relative proportion of α-helix and β-sheet in a protein can be measured by circular dichroism spectroscopy. Discrepancies between the observed and the predicted data can argue against a model structure. The precise cross-linking of the polypeptide chain through disulfide bridges or other chemical reagents provides distance constraints that connect sequentially distant regions of the chain. To a lesser extent, site directed mutagenesis, which detects the impact of changes to the amino acid sequence on protein stability and function, and limited proteolysis experiments, which detect the relative accessibility of regions of the chain, can provide useful constraints to sort between alternative model structures. The combination of theoretical methods and low-resolution experimental tools holds great promise for directing the construction of useful protein structure models. PREDICTING HIV PROTEASE STRUCTURE:AN EXCURSION Several types of proteases, enzymes that catalyze the breakdown of proteins, have been characterized by biochemists. Frequently, they are named after a key component of their catalytic machinery: serine, cysteine, aspartyl, or metallo proteases. With the discovery of the AIDS virus (HIV) and the determination of its genomic sequence, it appeared that the virus produced a great deal of its enzymatic and regulatory machinery as one long incapacitated polyprotein that required a specific protease to split it into active components. Sequence analysis suggested