The three-dimensional structure of a protein is a complex, exquisitely fashioned molecular ideogram, involving interactions among thousands (often tens or hundreds of thousands) of atoms. Each protein has only one native conformation, and, we want to know what it is because, for a protein molecule, function follows form. That is, a protein's biological role is a consequence of its conformation. A universal molecular grammar specifies protein conformation. This assertion is based on a telling experiment, the Anfinsen experiment. While the experiment convinced biochemists that such a grammar must exist, a level of understanding sufficient to predict protein conformation is still lacking; and that is the protein folding problem. The protein folding problem has emerged as one of the great scientific challenges of this century. The solution to this problem is critical to an understanding of the naturally occurring proteins and their deliberately engineered counterparts. Dr. Rose's principal goal is to elucidate the stereochemical code that governs protein folding and use it to formulate a practical folding algorithm. To this end, he is developing an algorithm, LINUS, to predict the fold of a protein from its amino acid sequence alone. LINUS is an acronym for Local Independently Nucleated units of Structure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of an extremely simple energy function. Current results are encouraging.
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