We have developed a new method, heterogeneous self-consistent ensemble optimization (hetero-SCEO), to select appropriate hydrophobic cores of proteins. It has been tested with five kinds of proteins: lambda-repressor, phage 434 CRO protein, interleukin-4, thioredoxin and ubiquitin. The results show that the method can be used for the de novo desigh of the hydrophobic cores of proteins.
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