HELIX PROPENSITY OF ALA AND VAL - A FREE-ENERGY PERTURBATION STUDY

Difference in helix propensity between Ala and Val was examined by a m olecular dynamics/free energy perturbation method. Simulations were ba sed on a simple two state model of helix-coil transition. Val10 in an Ala based 17mer peptide (Y1K2A3A4A5A6K7A8A9V10A11K12A13A14A15A16K17) u sed as the alpha-helical model, or in an extended trimer (A9V10A11) us ed as the random coil model, was perturbed to Ala by a slow growth met hod. The computed DELTADELTAG (-1.27 +/- 0.92 kcal/mol) reproduced sem iquantitatively the experimental DELTADELTAG (-0.7 kcal/mol; Padmanabh an et al., Nature 344 (1990) 268). Inclusion of intraperturbed contrib utions was essential. Free energy component analysis showed that intra -perturbed interaction within Val10 contributed positive value to DELT ADELTAG and that interaction between Lys7 and Val10 contributed negati ve value. The tatter dominated the former, which resulted in the large r helix propensity of Ala.