Helix propensity of Ala and Val: a free energy perturbation study.
Difference in helix propensity between Ala and Val was examined by a molecular dynamics/free energy perturbation method. Simulations were based on a simple two state model of helix-coil transition. Val10 in an Ala based 17mer peptide (Y1K2A3A4A5A6K7A8A9V10A11K12A13A14A15A16K17) used as the alpha-helical model, or in an extended trimer (A9V10A11) used as the random coil model, was perturbed to Ala by a slow growth method. The computed delta delta G (-1.27 +/- 0.92 kcal/mol) reproduced semiquantitatively the experimental delta delta G (-0.7 kcal/mol; Padmanabhan et al., Nature 344 (1990) 268). Inclusion of intraperturbed contributions was essential. Free energy component analysis showed that intra-perturbed interaction within Va10 contributed positive value to delta delta G and that interaction between Lys7 and Val10 contributed negative value. The latter dominated the former, which resulted in the larger helix propensity of Ala.
Molecular Physics Section, Agency of Industrial Science and Technology, Ibaraki, Japan.
Y
Y
Komeiji
N
N
Honda
I
I
Yamato
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D014633:Valine / Q000737:chemistry*
D010455:Peptides; D014633:Valine; D000409:Alanine