Document 0176
 DOCN  M9460176
 TI    Studies on the specificity of HIV protease: an application of Markov
       chain theory.
 DT    9404
 AU    Chou KC; Zhang CT; Upjohn Laboratories, Kalamazoo, Michigan 49001-4940.
 SO    J Protein Chem. 1993 Dec;12(6):709-24. Unique Identifier : AIDSLINE
       MED/94183407
 AB    A sequence-coupled (Markov chain) model is proposed to predict the
       cleavage sites in proteins by proteases with extended specificity
       subsites. In addition to the probability of an amino acid occurring at
       each of these subsites as observed from a training set of oligopeptides
       known cleavable by HIV protease, the conditional probabilities as
       reflected by the neighbor-coupled effect along the subsite sequence are
       also taken into account. These conditional probabilities are derived
       from an expanded training set consisting of sufficiently large peptide
       sequences generated by the Monte Carlo sampling process. Very high
       accuracy was obtained in predicting protein cleavage sites by both HIV-1
       and HIV-2 proteases. The new method provides a rapid and accurate means
       for analyzing the specificity of HIV protease, and hence can be used to
       help find effective inhibitors of HIV protease as potential drugs
       against AIDS. The principle of this method can also be used to study the
       specificity of any multisubsite enzyme.
 DE    Acquired Immunodeficiency Syndrome/DRUG THERAPY  Amino Acid Sequence
       Antiviral Agents/THERAPEUTIC USE  Aspartic Proteinases/*METABOLISM  Drug
       Design  Human  HIV Protease/*METABOLISM  HIV-1/ENZYMOLOGY
       HIV-2/ENZYMOLOGY  Markov Chains  Molecular Sequence Data  Monte Carlo
       Method  Peptide Fragments/*METABOLISM  Proteins/METABOLISM  Substrate
       Specificity  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).