Computational design of a protein crystal.

Protein crystals have catalytic and materials applications and are central to efforts in structural biology and therapeutic development. Designing predetermined crystal structures can be subtle given the complexity of proteins and the noncovalent interactions that govern crystallization. De novo protein design provides an approach to engineer highly complex nanoscale molecular structures, and often the positions of atoms can be programmed with sub-Å precision.

Tidal surge in the M2 proton channel, sensed by 2D IR spectroscopy.

The M2 proton channel from influenza A virus transmits protons across membranes via a narrow aqueous pore lined by water and a proton sensor, His37. Near the center of the membrane, a water cluster is stabilized by the carbonyl of Gly34 and His37, the properties of which are modulated by protonation of His37. At low pH (5-6), where M2 conducts protons, this region undergoes exchange processes on the microsecond to second timescale.

Structural and dynamic mechanisms for the function and inhibition of the M2 proton channel from influenza A virus.

The M2 proton channel from influenza A virus, a prototype for a class of viral ion channels known as viroporins, conducts protons along a chain of water molecules and ionizable sidechains, including His37. Recent studies highlight a delicate interplay between protein folding, proton binding, and proton conduction through the channel. Drugs inhibit proton conduction by binding to an aqueous cavity adjacent to M2's proton-selective filter, thereby blocking access of proton to the filter, and altering the energetic landscape of the channel and the energetics of proton-binding to His37.

Using two fluorescent probes to dissect the binding, insertion, and dimerization kinetics of a model membrane peptide.

Helix-helix association within a membrane environment represents one of the fundamental processes in membrane protein folding. However, studying the kinetics of such processes has been difficult because most membrane proteins are insoluble in aqueous solution. Here we present a stopped-flow fluorescence study of the membrane-interaction kinetics of a designed, water-soluble transmembrane (TM) peptide, anti-alpha(IIb), which is known to dimerize in phospholipid bilayers.

Biophysical and structural characterization of a robust octameric beta-peptide bundle.

Proteins composed of alpha-amino acids are essential components of the machinery required for life. Stanley Miller's renowned electric discharge experiment provided evidence that an environment of methane, ammonia, water, and hydrogen was sufficient to produce alpha-amino acids. This reaction also generated other potential protein building blocks such as the beta-amino acid beta-glycine (also known as beta-alanine); however, the potential of these species to form complex ordered structures that support functional roles has not been widely investigated.

Toward beta-amino acid proteins: a cooperatively folded beta-peptide quaternary structure.

Folded polymers in nature are assembled from simple monomers and adopt complex folded structures through networks of stabilizing noncovalent interactions. These interactions define secondary and tertiary structure and in most cases specify a unique three-dimensional architecture. Individual secondary or tertiary structures can also associate with one another to form multi-subunit quaternary structures.