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Amide-to-E-olefin versus amide-to-ester backbone H-bond perturbations: Evaluating the O-O repulsion for extracting
Yanwen Fu1, Jianmin Gao, Jan Bieschke
1Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, BCC 506, La Jolla, California 92037, USA.
Abstract:
Both amide-to-ester and amide-to-E-olefin backbone amide mutation methods were employed to perturb the same H-bond (formed by the NH of F23 and the CO of R14) in the Pin WW domain. Comparison of the thermodynamic folding energies of the ester mutant and the E-olefin mutant, accounting for the transfer free energy differences measured on relevant model compounds, yielded an estimated value of 0.3 kcal/mol for the O-O repulsion term (DeltaGO-Orep) in a beta-sheet context. The value of DeltaGO-Orep enabled us to calculate the intrinsic F23-R14 H-bond free energy to be 1.3 kcal/mol.
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