Probabilistic, Thermodynamic, and Information-Theoretic Constraints on De Novo Protein Assembly

This review quantifies the mathematical, stereochemical, and thermodynamic barriers to unguided de novo protein assembly. Combining sequence-space density (10^{-77}), L-amino acid homochirality (10^{-46}), and \alpha-peptide bond specificity (10^{-45}) yields a single-trial probability of 10^{-164} to 10^{-167} for a 150-residue protein—exceeding five-billion-year terrestrial trial limits (\le 10^{85}) by 10^{-79}. Alongside aqueous hydrolysis equilibria and Eigen’s error-catastrophe threshold, these constraints support an abductive inference toward Intelligent Design.