We discuss a general method for protein design based on an analysis in sequence space of the Boltzmann weight for a given target structure. An efficient Monte Carlo code that explores sequence space (and, for each sequence, the space of compact and noncompact conformations) is implemented and tested in two models in two dimensions which are amenable to an exact solution---the design procedure is always successful.
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Seno et al. (1996) studied this question.
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