Viral diseases have, for a number of reasons, eluded the sorts of broadly effective antibiotic treatments available for bacteria, and relatively few can be prevented by vaccinations. The long-term goal of this project is to design and produce soluble, high affinity T cell receptors (TcR) or TcR-like proteins (e.g., antibodies) targeting clinically important Major Histocompatibility Complexes (MHC)-peptide structure. Such TcR or TcR-like molecules can be used directly for in vitro diagnostics of viral infection, and can be combined with toxins to kill virally infected cells specifically. The goal of Phase I of this project is to apply recently developed computational methods for binding free energy minimization to the design of high affinity TcR for MHC-peptide complexes. The computational algorithms and software implemented and validated in Phase I will be used to design novel TcR sequences, which will be produced in Phase II of the project.
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