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A typical protein structure is a compact packing of connected [alpha]-helices and/or [beta]-strands. We have developed a method for generating the ensemble of compact structures a given set of helices and strands can form. The method is tested on structures composed of four [alpha]-helices connected by short turns. All such natural four-helix bundles that are connected by short turns seen in nature are reproduced to closer than 3.6 [Angstrom] per residue within the ensemble. Because structures with no natural counterpart may be targets for ab initio structure design, the designability of each structure in the ensemble--defined as the number of sequences with that structure as their lowest-energy state--is evaluated using a hydrophobic energy. For the case of four [alpha]-helices, a small set of highly designable structures emerges, most of which have an analog among the known four-helix fold families; however, several packings and topologies with no analogs in protein database are identified.

Research demonstrates the association of complementing polar groups with buried and surface positions of proteins in protein folding as exemplified by a two-stranded coiled-coil design of the ACID-p1/BASE-p1 heterodimer. Data indicate that position-a Lys residues and Lys-Glu polar interactions impart a high level of structural feature to the heterodimer.

A nondegenerative recognition code table based on amino acid-DNA base interactions in DNA complexes with DNA-binding proteins is presented. The code table can be used to identify the specific amino acid, at a specific position of the alpha-helical region of zinc-finger domain, from the overlapping target sequence in a given DNA target.

Research suggests that the open and closed conformations of maltose-binding protein facilitate variable copper-copper distance formation. A mutation in the hinge region of the protein leads to the formation of a binuclear copper center, which simulates oxy-hemocyanin upon reacting with hydrogen peroxide.

Because of recent high-yield native ligation techniques, chemical synthesis of larger multidomain bioactive proteins is rapidly coming within reach. Here we describe the total chemical synthesis of a designed 'microprotein S,' comprising the [Gamma]-carboxyglutamic acid-rich module, the thrombin-sensitive module, and the first epidermal growth factor-like module of human plasma protein S (residues 1-116). Synthetic microprotein S expressed anticoagulant cofactor activity for activated protein C in the down-regulation of blood coagulation, and the anticoagulant activity of microprotein S was not neutralized by C4b-binding protein, a natural inhibitor of native protein S in plasma. The correct folding of this complex multidomain protein was enhanced compared with individual modules because the [Gamma]-carboxyglutamic acid-rich module and the thrombin-sensitive module markedly facilitated correct folding of the first epidermal growth factor-like module compared with folding of the first epidermal growth factor-like module alone. These results demonstrate that total chemical synthesis of proteins offers an effective way to generate multidomain biologically active proteins.

Barrel-like protein architectures support a wide range of biological functions, from transport across membranes to catalysis of metabolic reactions. Previously, Baumeister and Matile synthesized tetrameric barrels that self-assemble from solution [...]