The invention relates to a method for detecting the proximity of at least two biomolecules using branched DNA technology. The assay is called branched proximity hybridization assay.

The present disclosure provides sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

The present invention relates to methods and kits for detection protein-protein interactions. In particular, the present invention relates to a method for detecting the binding between a first polypeptide (A) and a second polypeptide (B) in a cell comprising i) providing a cell that expresses (a) a polypeptide (GFP1-9) comprising an amino acid sequence having at least 90% of identity with the amino acid sequence selected from the group consisting of SEQ ID NO: 1-4 (b) a first fusion protein wherein the polypeptide (A) is fused to a polypeptide (GFP10) having an amino an amino acid sequence having at least 90% of identity with the amino acid sequence selected from the group consisting of SEQ ID NO:5-7 (c) a second fusion protein wherein the polypeptide (B) is fused to a polypeptide (GFP11) having an amino an amino acid sequence having at least 90% of identity with the amino acid sequence selected from the group consisting of SEQ ID NO: 8-9 and (d) an intrabody specific for the complex formed by the self-assembly of the first, second and third polypeptides (a), (b) and (c) ii) detecting the fluorescence wherein when the fluorescence is detected it is concluded that the polypeptide (A) binds to polypeptide (B) and wherein the fluorescence is not detected it is concluded that the polypeptides (A) does not bind to polypeptide (B).

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.

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.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Methods are disclosed for identifying one or more proteins or polypeptides comprised by a sample. The methods comprise determining binding of each polypeptide with respect to each binding pool of a plurality of binding pools, wherein each binding pool comprises one or more probes which bind a structure comprised by a protein or polypeptide. In some aspects, polypeptides can be denatured and separated into individual polypeptide strands and immobilized on a solid support prior to determining binding of the binding pools. A protein, polypeptide or polypeptide strand can be identified by searching, in at least one database, for a protein or polypeptide sequence comprising binding pool targets either identical to or most similar to the binding pool targets comprised by the protein, polypeptide or polypeptide strand to be identified. Kits for identifying proteins, polypeptides and polypeptide strands are also disclosed.

A method for determining protein binding specificity using a screen of a peptide library is provided. The method can be used to determine binding specificity for human NAD.sup.+-dependent deacetylase SIRT1, and to identify the most efficiently deacetylated peptide sequences. The method can be also used to screen a combinatorial H4 histone N-terminal tail peptide library to examine the binding preferences of a -phos (S1) H4 antibody toward all known possible H4 histone modification states.

Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

The present invention relates to a method for the production of a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 as well as a method for selecting from a library comprising recombinant derivatives of the SH3 domain of the Fyn kinase of SEQ ID NO: 1 one or more of said derivatives having a specific binding affinity to a protein or peptide.