The invention relates to a method for determining levels of interactions between biomolecules, such as proteins, in a sample, comprising providing a first and a second information carrying (IC) oligonucleotide, wherein the first and second IC oligonucleotide are attached, covalently or non-covalently, to a first and a second affinity reagent, such as antibodies, that have the capacity to bind to a first and a second biomolecule, wherein the first and second IC oligonucleotide each comprises at least one single-stranded stretch that is complementary to a part of another oligonucleotide, thereby, upon hybridisation of the at least one single-stranded stretch in at least one of the first and second IC oligonucleotides to its complementary part of another oligonucleotide, enabling measurement of the relative proportion of interacting and non-interacting first and second biomolecules in the sample at a single cell or single molecular level. Further, the invention relates to kits including necessary oligonucleotides and reagents to carry out the method of the invention.

Disclosed is a method that combines high throughput and flexible nature of a cell-free protein microarray with the quantitative capability of surface plasmon resonance to detect >400 different protein interactions in <1 hour. A method of detecting interactions between a targeting agent and one or more proteins of interest is disclosed. The method includes producing a set of proteins of interest using a cell-free protein expression system; providing the set of proteins of interest on a protein microarray wherein each spot in the array comprises a protein of interest; contacting the protein microarray with a targeting agent that binds to one or more of the set of proteins of interest; and detecting the binding of the targeting agent to the set of proteins of interest using surface plasmon resonance imaging (SPRi), thereby detecting the targeting agent and one or more proteins of interest in the micro array.

Methods for in situ detecting proximity of two targets of interest featuring an antibody conjugated with a cleavable bridge component having a detectable moiety and an antibody conjugated with a non-cleavable bridge component. The bridge components each have a chemical ligation group adapted to form a covalent bond under particular conditions and when the targets are in close proximity. Following covalent bond formation, the cleavable bridge component can be cleaved from the antibody, effectively transferring the detectable moiety to the non-cleavable bridge component. Detection of the detectable moiety is indicative of the targets being in close proximity. The methods are compatible with both chromogenic and fluorogenic detection systems. The methods may be used to perform assays wherein one or more than one proximity event is detected on the same slide.

The present invention generally relates to bacterial polypeptide display systems, libraries using these bacterial display systems, and methods of making and using these systems, including methods for improved display of polypeptides on the extracellular surface of bacteria using circularly permuted transmembrane bacterial polypeptides that have been modified to increase resistance to protease degradation and to enhance polypeptide display characteristics.

Systems and methods for obtaining qualitative or quantitative measurements of proteoforms of polypeptides are described. The described methods include measurements of affinity reagent binding on single-molecule polypeptide arrays to distinguish between polypeptide isoforms. The described methods may provide high resolution quantitative comparisons of proteoforms with very low copy numbers.

This application provides an improved screening method for the selection of target-binding proteins having desirable biophysical properties. The method combines mRNA display and yeast surface display in a way that takes advantage of the desirable attributes of both processes.

The invention relates to methods for conducting solid-phase binding assays. One example is an assay method having improved analyte specificity where specificity is limited by the presence of non-specific binding interactions.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Methods and compositions are disclosed for rapid functional analysis of gene variants based on analysis of protein-protein and protein-nucleic acid interactions.

A method for analyzing macromolecules, including peptides, polypeptides, and proteins, employing nucleic acid encoding is disclosed.