Design principles of protein switches |
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| Institution: | 1. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA;2. UC Berkeley–UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA;3. Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA;1. Department of Biochemistry, University of Washington, Seattle, WA, USA;2. Institute for Protein Design, University of Washington, Seattle, WA, USA;3. Independent researcher, Haifa, Israel;1. Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA;2. Stanford ChEM-H, Stanford University, Stanford, CA, 94305, USA;3. Microsoft Research New England, Cambridge, MA, 02142, USA |
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| Abstract: | Protein switches perform essential roles in many biological processes and are exciting targets for de novo protein design, which aims to produce proteins of arbitrary shape and functionality. However, the biophysical requirements for switch function — multiple conformational states, fine-tuned energetics, and stimuli-responsiveness — pose a formidable challenge for design by computation (or intuition). A variety of methods have been developed toward tackling this challenge, usually taking inspiration from the wealth of sequence and structural information available for naturally occurring protein switches. More recently, modular switches have been designed computationally, and new methods have emerged for sampling unexplored structure space, providing promising new avenues toward the generation of purpose-built switches and de novo signaling systems for cellular engineering. |
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