WHAT MAKES A PROTEIN-A PROTEIN - HYDROPHOBIC CORE DESIGNS THAT SPECIFY STABILITY AND STRUCTURAL-PROPERTIES

Here we describe how the systematic redesign of a protein's hydrophobi c core alters its structure and stability. We have repacked the hydrop hobic core of the four-helix-bundle protein, Rop, with altered packing patterns and various side chain shapes and sizes. Several designs rep roduce the structure and native-like properties of the wildtype, while increasing the thermal stability. Other designs, either with similar sizes but different shapes, or with decreased sizes of the packing res idues, destabilize the protein. Finally, overpacking the core with lar ger side chains causes a loss of native-like structure. These results allow us to further define the roles of tight residue packing and the burial of hydrophobic surface area in the construction of native-like proteins.