A strategy of logical drug design (LDD) and its application to prion diseases are reviewed. LDD is primarily
based on the localizability of a hot spot which initiates structural instability in the target protein. It is also based on the
regulability of the hot spot by small compounds, their designabilty by a computer, their organic synthesizability and the
specificity of their functions once administered to the biological organisms. Unification of localizability, regulability, producibility
and specificity is the central theme of LDD. Theoretical foundation of LDD based on quantum theories is initially
outlined. The localizability using nuclear magnetic resonance (NMR), the regulability by a medical chaperone, the
synthesizability, and the functional specificity accomplished thus far, are then described.
Keywords: Logical drug design, quantum chemistry, prion, hot spot, medical chaperone.
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