Energetics of the interaction between water and the helical peptide group and its role in determining helix propensities

摘要

The alanine helix provides a model system for studying the ener- getics of interaction between water and the helical peptide group, a possible major factor in the energetics of protein folding. Helix formation is enthalpy-driven (-1.0 kcal/mol per residue). Experi- mental transfer data (vapor phase to aqueous) for amides give the enthalpy of interaction with water of the amide group as ≈ -11.5 kcal/mol. The enthalpy of the helical peptide hydrogen bond. computed for the gas phase by quantum mechanics, is -4.9 kcal/mol. These numbers give an enthalpy deficit for helix forma- tion of -7.6 kcal/mol. To study this problem, we calculate the electrostatic solvation free energy (ESF) of the peptide groups in the helical and β-strand conformations, by using the DELPHI program and PARSE parameter set. Experimental data show that the ESF values of amides are almost entirely enthalpic. Two key results are: in the β-strand conformation. the ESF value of an interior alanine peptide group is -7.9 kcal/mol. substantially less than that of N-methylacetamide (-12.2 kcal/mol), and the helical peptide group is solvated with an ESF of -2.5 kcal/mol. These results reduce the enthalpy deficit to -1.5 kcal/mol, and desolvation of peptide groups through partial burial in the random coil may account for the remainder. Mutant peptides in the helical confor- mation show ESF differences among nonpolar amino acids that are comparable to observed helix propensity differences, but the ESF differences in the random coil conformation still must be subtracted.