# A novel directed evolution platform for engineering chemically gated protein switches

## TL;DR

The paper introduces a new platform for engineering protein switches that respond to chemicals, using yeast to efficiently select functional variants.

## Contribution

The novel DuoSelect platform combines positive and negative selection in a single sorting round to improve the efficiency of protein switch engineering.

## Key findings

- DuoSelect uses two-color fluorescence to enrich high signal-to-background protein switch variants.
- The platform successfully selected two chemical-dependent protein switches for cellular assays.
- The method enables rapid isolation of functional chemically gated protein switches.

## Abstract

Chemically gated protein switches have broad applications in regulating cellular activities. In this study, we introduce DuoSelect, a yeast surface selection platform for selecting protein switches based on signal-to-background ratios by combining both negative and positive selections in a single round of sorting. We demonstrate this platform's utility by selecting for two chemical-dependent protein switches and showcase the protein switch's application in cellular assays.

DuoSelect is a yeast surface display platform for rapid isolation of chemically gated protein switches. It integrates positive and negative selection in one round by two-color fluorescence readout, enriching high signal-to-background variants.