In some embodiments, the invention relates to methods and reagents for the identification of compounds that traverse he cell membrane of an animal cell. In some embodiments, the invention provides additional methods for determining if a candidate compound that traverses an animal cell membrane is able to modulate an intracellular target, as well as reagents and kits for reagents and kits for performing the disclosed methods.

The disclosure provides for artificial signal peptides generated by systems and methods utilizing deep learning.

Provided herein are reagents and methods for incorporating modified nucleotides into DNA and detecting DNA synthesis. In particular, haloalkyl-modified nucleobases are provided for incorporation into nucleic acids for detection by bioluminescent binding agents.

A voltage indicator includes a polypeptide sequence comprising a voltage-sensitive opsin domain and a capture protein domain arranged and disposed to capture a fluorescent dye ligand. When the fluorescent dye ligand is captured and the voltage indicator is bound to a cell membrane, an increase in voltage across the cell membrane causes an increase in fluorescent emission.

Provided herein are substantially non-luminescent peptide/polypeptide tags that are inserted internally within a protein of interest or between N-terminal and C-terminal peptides/polypeptides. Interaction of the internally-inserted tag with a complement polypeptide/peptide that is also substantially non-luminescent results in the formation a bioluminescent reporter complex.

Provided herein are substantially non-luminescent peptide/polypeptide tags that are inserted internally within a protein of interest or between N-terminal and C-terminal peptides/polypeptides. Interaction of the internally-inserted tag with a complement polypeptide/peptide that is also substantially non-luminescent results in the formation a bioluminescent reporter complex.

The present invention provides a fusion protein of an antigen-binding protein and a fluorescent protein or a fluorescence-labeled tag protein. The present invention provides a fusion protein of an antigen-binding protein and a fluorescent protein or a fluorescence-labeled tag, wherein the antigen-binding protein is an antigen-binding protein having a helix structure or a β-sheet structure at a terminus, the fluorescent protein or the fluorescence-labeled tag is a fluorescent protein or a fluorescence-labeled tag having a helix structure or a β-sheet structure at a terminus, and the helix at the terminus and the helix at the terminus are linked, or the β-sheet structure at the terminus and the β-sheet structure at the terminus are linked.

A voltage indicator includes a polypeptide sequence comprising a voltage-sensitive opsin domain and a capture protein domain arranged and disposed to capture a fluorescent dye ligand. When the fluorescent dye ligand is captured and the voltage indicator is bound to a cell membrane, an increase in voltage across the cell membrane causes an increase in fluorescent emission.

Provided herein are a voltage indicator and a method of measuring voltage. The voltage indicator includes a membrane-localized voltage-sensitive protein coupled to a capture protein. The method of measuring voltage includes administering a voltage indicator including a membrane-localized voltage-sensitive protein coupled to a capture protein, and determining changes in fluorescence of a small-molecule fluorescent dye captured by the capture protein.

The invention relates to a modular polypeptide comprising a first partial effector sequence comprising a first part of a circular permutated halotag protein connected to a sensor module sequence, which is connected to a second part of a circular permutated halotag protein. The sensor module is a single polypeptide or a polypeptide pair capable of undergoing conformational change from a first confirmation to a second confirmation depending on the presence or concentration of an analyte compound. The modular peptide is catalytically active in response to an environmental stimulus or in response to the sensor pair interacting.

The invention further relates to nucleic acid sequences encoding the modular polypeptide, and to kits comprising same.