Homework

Weekly homework submissions:

• Week 1 HW: Principles and Practices

  Class Assignment This assignment was done with the help of AI Engineering Allosteric Proteins via Domain Insertion I am interested in developing a computational tool to identify stable domain‐insertion sites for creating novel allosteric proteins. In this approach, a functional protein domain (e.g. a sensor or light‐sensing domain) is inserted into another protein, so that a change in the sensor domain (triggered by a ligand, light, etc.) allosterically controls the host protein’s activity. This strategy can produce “protein switches” with new-to-nature functions. For example, Wolf et al. (2025) demonstrated that domain insertion can generate potent optogenetic or chemogenetic switches: they built a machine‐learning pipeline (ProDomino) to predict insertion sites, and successfully created light‐ and ligand‐activated versions of proteins (including Cas9 variants) by inserting receptor domains. In general, computational protein design is rapidly improving, especially with AI methods, and promises to transform biotechnology and medicine. A dedicated tool for domain-insertion design would accelerate development of custom allosteric proteins (for biosensors, therapeutics, metabolic control, etc.) by predicting which residues can accept an insert without misfolding. Such a tool would integrate protein structure modeling, stability prediction, and sequence‐function data, guiding one-shot design of switchable proteins as described in recent literature.