Design of De Novo Beta-Sheet Proteins.

摘要

The goal of the proposed research was to design combinatorial libraries of de novo beta-sheet proteins. The design of these libraries was based on a binary code strategy, which specifies the sequence locations of polar and nonpolar amino acids, but allows the exact identities of the amino acid side chains to be varied combinatorially. The binary code strategy is made possible by the organization of the genetic code, which uses NAN codons to encode polar amino acids and NTN codons to encode nonpolar amino acids (N denotes a mixture of the DNA bases A, G, C & T). The initial research proposal focused on designing libraries of soluble monomeric beta-sheet proteins. In the intervening years the authors have achieved this goal. They also have achieved several additional goals not outlined in the original proposal. Specifically, they have constructed several collections of de novo beta-sheet proteins. Among these collections are proteins that do the following: (1) fold intramolecularly as monomers in aqueous solution, (2) self-assemble into amyloid-like fibrils, (3) assemble into monolayers at an air/water interface, and (4) form ordered structures templated by inorganic surfaces. Collections 2 and 3 were published during the earlier years of the project West et al. (1999) PNAS 96, 11211; Broome & Hecht (2001) J. Mol. Biol. 296, 961; and Xu et al. (2001) PNAS 98, 3652. Collection 1 was published recently Wang & Hecht (2002) PNAS 99, 2760. Collection 4 also was published recently Brown, Aksay, Saville & Hecht (2002) J. Am. Chem. Soc. 124, 6846. (8 figures, 6 refs.).