Computationally Designed Prion-Like Protein Systems
Abstract
We propose to design synthetic prion-like proteins for signal amplification that assemble into long fibers in the presence, but not the absence of a nucleant. Signal amplification using such a synthetic prion approach has the potential for considerably higher sensitivity and specificity than current methods as nucleation can be tightly controlled and the fibers can grow to more than 1,000 monomers in length. The innovation in our approach is to use synthetic proteins in which assembly can be controlled such that fibers form in the presence, but not the absence of nucleant. The key technical challenge is to compute new protein molecules with sufficient accuracy that nucleation is absolutely dependent on the presence of the nucleant. Our long-term vision is to develop general and robust methods for designing protein-based molecular signal amplification systems that are faster, more sensitive, more specific, and more robust that standard nucleic acid amplification procedures. By designing each element of these prion-like fiber forming materials from the bottom up, we will enable an unprecedented level of control and customization regarding their structures and functions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 06, 2018
- Source ID
- W911NF1710318
Entities
People
- David Baker
Organizations
- Army Contracting Command
- Office of the Secretary of Defense
- University of Washington