Computational design of a sensitive, selective phase-changing sensor protein for the VX nerve agent.

ABSTRACT: The VX nerve agent is one of the deadliest chemical warfare agents. Specific, sensitive, real-time detection methods for this neurotoxin have not been reported. The creation of proteins that use biological recognition to fulfill these requirements using directed evolution or library screening methods has been hampered because its toxicity makes laboratory experimentation extraordinarily expensive. A pair of VX-binding proteins were designed using a supercharged scaffold that couples a large-scale phase change from unstructured to folded upon ligand binding, enabling fully internal binding sites that present the maximum surface area possible for high affinity and specificity in target recognition. Binding site residues were chosen using a new distributed evolutionary algorithm implementatio

SUBMITTER: McCann JJ 

PROVIDER: S-EPMC9258810 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature