Globular proteins are characterized by the specific and tight packing of hydrophobic side-chains in the so-called "hydrophobic core." Formation of the core is key in folding, stabilization, and conformational specificity. The critical role of hydrophobic cores in maintaining the highly ordered structures present in natural proteins justifies the tremendous efforts devoted to their redesign. Both experimental and computational combinatorial-based approaches have been reported in the last years as powerful protein design tools. These manage to explore large regions of the sequence/conformational space, allowing the search for alternative protein core arrangements displaying native-like properties. The overall results obtained from core design projects have contributed significantly to our present knowledge of protein folding and function. In addition, core design has worked as a benchmark for the development of ambitious protein design projects that nowadays are allowing the de novo design of novel protein structures and functions.
Copyright 2004 Wiley-Liss, Inc.