Detection of molecular associations

1. A method of detecting an association between a query protein and a target moiety, the method comprising:

providing the query protein comprising a tag and a barcode; wherein

the barcode comprises a polynucleotide comprising a coding sequence of the query protein;

contacting the query protein with a composition comprising the target moiety, whereby the target moiety associates with the query protein;

applying a crosslinking agent or force to the query protein and the composition, thereby crosslinking the query protein to the target moiety associated therewith;

covalently binding the tag to a substrate, thereby covalently immobilizing the query protein and crosslinked target moiety on the substrate;

washing the immobilized query protein and crosslinked target moiety under denaturing conditions, wherein the query protein remains immobilized on the substrate; and

detecting the target moiety associated with the query protein after said washing.

2. The method of claim 1 , wherein the method is performed in multiplex, comprising two or more different query proteins, each comprising a different barcode.

3. The method of claim 1 , wherein the barcode comprises a covalent polypeptide tag fused to the polynucleotide, and wherein said covalent polypeptide tag is covalently bound to a counterpart polypeptide sequence on the query protein.

4. The method of claim 3 , wherein the counterpart polypeptide sequence is disposed at an N terminus of the query protein.

5. The method of claim 3 , wherein the covalent polypeptide tag and counterpart polypeptide sequence comprise a Spytag and SpyCatcher; or Isopeptag and pilin-C; or SnoopTag and SnoopC-atcher; or DogTag and SnoopTagJr; or SdyTag and SdyCatcher.

6. The method of claim 3 , wherein providing the query protein comprises:

fusing the covalent polypeptide tag to the polynucleotide encoding the query protein, wherein the counterpart polypeptide sequence is disposed at an N-terminal portion of the query protein;

transcribing the polynucleotide in vitro, thereby producing the query protein comprising the counterpart polypeptide sequence disposed at the N-terminal portion and further comprising the tag; and

covalently binding the polypeptide tag to the counterpart polypeptide sequence, thereby making the query protein comprising the tag and the barcode.

7. The method of claim 1 , wherein the contacting and applying are in vivo.

8. The method of claim 7 , wherein providing the query protein comprising the tag comprises expressing a nucleic acid encoding the query protein comprising the tag in vivo.

9. The method of claim 8 , further comprising administering a vector comprising the nucleic acid encoding the query protein comprising the tag to a cell.

10. The method of claim 1 , wherein:

the tag comprises a haloalkane dehalogenase and the substrate comprises a haloalkane resin; or

the tag comprises a DNA methyltransferase and the substrate comprises a benzylguanine resin; or

the tag comprises a DNA methyltransferase and the substrate comprises a benzylcytosine resin; or

the tag comprises an isopeptag and the substrate comprises a pilin-C protein; or

the tag comprises a SpyTag and the substrate comprises a SpyCatcher protein; or

the tag comprises SnoopTag and the substrate comprises a SnoopCatcher protein; or

the tag comprises DogTag and the substrate comprises SnoopTagJr; or

the tag comprises SdyTag and the substrate comprises SdyCatcher; or

the tag comprises Cpe0147 565-587 and the substrate comprises Cpe0147 439-563 .

11. The method of claim 1 , wherein the target moiety is a protein, a nucleic acid, or a protein-nucleic acid complex.

12. The method of claim 1 , wherein the target moiety comprises an RNA, and wherein the washing is at a temperature effective to fragment RNA, thereby fragmenting the target moiety.

13. The method of claim 1 , wherein the crosslinking agent or force comprises ultraviolet radiation, or an amine-to-amine crosslinker, or a sulfhydryl-to-sulfhydryl crosslinker, or an aryl-azide, or a diazirine.

14. The method of claim 1 , wherein covalently binding the tag to the substrate and washing are performed in a single container.

15. A composition comprising

a query protein comprising a tag and a barcode; wherein

the barcode comprises a polynucleotide comprising a coding sequence of the query protein;

a substrate, wherein the tag is covalently bound to the substrate;

a target moiety crosslinked to the query protein;

wherein the composition is under denaturing conditions.

16. The composition of claim 15 , wherein the barcode comprises a covalent polypeptide tag fused to the polynucleotide, and wherein said covalent polypeptide tag is covalently bound to a counterpart polypeptide sequence on the query protein.