Abstract: Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

Abstract: Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

Abstract: The preset disclosure provides chimeric polypeptides comprising a cage polypeptide comprising a degron, wherein the degron is sequestered or caged. Upon activation by a key polypeptide, the degron becomes active. The degron can recruit an ubiquitin ligase and a lysine in the degron or surrounding sequence be ubiquitinated. The ubiquitinated chimeric polypeptide is marked for degradation, together with any biologically active molecule attached to the chimeric polypeptide. The chimeric polypeptides of the present disclosure can be incorporated, for example, to chimeric antigen receptors (CAR). Accordingly, in response to the administration of a key polypeptide or endogenous expression of a key polypeptide mediated, for example, by an inducible promoter, the amount of CAR expressed on the surface of an immune cell can be modulated.

Abstract: Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.

Abstract: The present disclosure provides a chimeric polypeptide comprising a helical bundle which comprises between about two and about seven alpha-helices and a bioactive peptide, wherein one or more of the alpha helices form one or more inter-helix hydrogen bonds and comprise at least one phosphorylation site and wherein the bioactive peptide is conformationally placed inside the helical bundle so that the bioactive peptide is not activated or exposed. The disclosure also provides a nucleotide sequence encoding the chimeric polypeptide, a vector comprising the nucleotide sequence, a cell comprising the nucleotide sequence, and method of making, using, or designing the chimeric polypeptide.

Abstract: Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain only when the protein switch components are co/localized when bound to their targets, components of such protein switches, and their use.

Abstract: Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.

Abstract: Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

Abstract: Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypep-tides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

Abstract: Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

Abstract: Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

Abstract: Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

Abstract: Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

Abstract: Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

Abstract: Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

Abstract: Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

Abstract: Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.