Disclosed is a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, wherein an antigen-binding domain in each of the antigen-binding molecules comprises at least one amino acid residue that changes the antigen-binding activity of the antigen-binding molecule depending on ion concentration conditions. Also disclosed are a composition comprising a plurality of polynucleotide molecules each encoding the antigen-binding molecules, a composition comprising a plurality of vectors each comprising the polynucleotide molecules, a method for selecting the antigen-binding molecules, a method for isolating the polynucleotide molecules, a method for producing the antigen-binding molecules, and a pharmaceutical composition comprising any of the antigen-binding molecules.

Provided are methods for detecting protein interactions in a sample, the methods comprising: (a) detecting two or more polypeptides that when associated emit a first detectable signal in a first light emission spectrum; (b) contacting the two or more polypeptides with a third polypeptide conjugated to a dipole acceptor moiety that has a second light emission spectrum when excited within a light excitation spectrum, wherein the light excitation spectrum overlaps with the first light emission spectrum; and (c) detecting a second detectable signal emitted in the second light emission spectrum by the dipole acceptor moiety. Also provided are bioluminescent complexes comprising: (a) a first polypeptide conjugated to a dipole acceptor moiety, wherein the emits a first detectable signal in a first light emission spectrum.

The disclosure provides polypeptides, fusion proteins, kits, dimers, nucleic acids, expression vectors, or host cells for use hi chemically induced dimerization systems, exemplified by a chemically induced dimerization system in which two recombinant antibodies dimerize only in the presence of cannabidiol.

The invention relates to novel libraries of linear and cyclic peptides, and methods of generating and screening such libraries for biological, pharmaceutical and other uses.

A complementation system including two fragments of photoactive yellow protein (PYP), or truncated fragments thereof, and its use with a fluorogenic hydroxybenzylidene rhodanine (HBR) analog for detecting interactions between biological molecules of interest, in particular between proteins of interest. Especially, a complementation system including a first PYP fragment having an amino acid sequence having at least about 70% identity with the amino acid sequence of SEQ ID NO: 23, or a truncated fragment thereof including at least 89 consecutive amino acids from the C-terminal end of the amino acid sequence; and a second PYP fragment having an amino acid sequence having at least about 70% identity with the amino acid sequence of SEQ ID NO: 34, or a truncated fragment thereof including at least 8 consecutive amino acids of the amino acid sequence, preferably 8 consecutive amino acids from the N-terminal end of the amino acid sequence.

The invention relates to a method for selecting a glycopolypeptide that binds to a target protein, the method including the steps of providing a pool of glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex; combining the pool with a target protein to form a mixture; incubating the mixture for a period of time sufficient to allow any target protein to bind to one or more of the glycopolypeptides, thereby forming glycopolypeptide-target protein complexes; and isolating from the mixture the glycopolypeptide-target protein complexes, thereby identifying a plurality of selected glycopolypeptides.

Described herein are methods and systems useful for interrogating protein-protein interactions. These systems utilize non-functional fragments of polypeptides that can complement each other to form a fully functional fragment in vivo. The fully functional polypeptide releases a transcription regulating polypeptide that can bind and activate or repress a reporter element.

High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.

The present disclosure relates to methods of inhibiting vimentin activity, methods of screening for new vimentin inhibitors and uses of new vimentin inhibitors.

A method for screening for a polypeptide that acts on a target protein, including (1) providing a polynucleotide library constituted of a plurality of expression vectors that can be expressed in a gram-negative bacterium, where the plurality of expression vectors each include a first polynucleotide encoding a polypeptide different from one another, a secretory signal sequence positioned upstream of the first polynucleotide, and a second polynucleotide encoding a target protein, (2) transforming a gram-negative bacterium with the expression vector to express the polypeptide in a periplasmic space and the target protein on an inner membrane surface, (3) contacting the polypeptide with the target protein in the periplasmic space, (4) allowing the gram-negative bacterium to form a spheroplast to measure activity of the polypeptide on the target protein by a patch clamp technique, and (5) identifying the polypeptide that acts on the target protein based on the measured activity.