| Institution: | 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. Bioinformatics Program, Boston University, United States;2. Dept. of Biochemistry, Boston University, United States;1. UCLA Department of Chemistry and Biochemistry, United States;2. UCLA-DOE Institute for Genomics and Proteomics, United States;3. UCLA-Molecular Biology Institute, United States;1. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA;2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27514, USA;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 |
| Abstract: | Nature has evolved a vast repertoire of structures and functions based on an ordered, orchestrated, protein building-blocks assembly. For decades these sophisticated materials have been studied, mimicked, and repurposed, yet recently, computational protein engineering methods provided an alternative route: creating protein materials de-novo, surpassing evolutionary constraints and optimized for specific tasks. We highlight two areas of research that fundamentally accelerate design of structurally well-defined programmable protein materials. First, implementations of hierarchical assembly and geometric sampling (docking) strategies to create designable backbones under pre-specified symmetry constraints. Second, progress in protein–protein interfaces and sequence design methods, using Rosetta, that drive programmable supramolecular assemblies. These approaches have proven effective in generating diverse protein assemblies in 0-, 1-, 2-, and 3-dimensional architectures (constituting single or multiple components), and as part of a synthetic or a biological system. We expect these methods shall transform the toolbox of protein designers developing next generation synthetic and biological materials. |
