Modeling of folding and unfolding mechanisms in alanine-based α-helical polypeptides Article

Morozov, AN, Sheng, HL. (2006). Modeling of folding and unfolding mechanisms in alanine-based α-helical polypeptides . JOURNAL OF PHYSICAL CHEMISTRY B, 110(41), 20555-20561. 10.1021/jp061781e

cited authors

  • Morozov, AN; Sheng, HL

authors

abstract

  • α-Helix formation is known to be opposed by the entropy loss due to the folding and favored by the energy of molecular interactions. However, the underlying mechanism of these factors is still being discussed. Here we have used the experimental and calculation data for short alanine-based peptides embedded in water to model the mechanism of helix folding and unfolding and to calculate microscopically the free energy factors of alanine in the frame of helix coil conformational integrals. Classical helix-coil transition theories take into account the interactions in a peptide chain only if the i, i + 3 peptide bond participates in hydrogen bonding. But quantum mechanical calculations showed that interactions of the. i, i + 2 peptide bond play an important role in helix folding too. We also included the short-range repulsive interactions due to molecular steric clashes and the end effects due to polar/hydrogen-bonding interactions at the N and C termini. The helix and coil regions of peptide conformational space were defined using an experimental steric criterion for hydrogen bonding. Arginine helix propensity was discussed and estimated. Monte Carlo numerical simulations of thermodynamics and kinetics for the 21 amino acid α-helical polypeptide Ac-A5(AAARA) 3A-NMe were carried out and found to be in an agreement with the experimental results. © 2006 American Chemical Society.

publication date

  • October 19, 2006

published in

Digital Object Identifier (DOI)

start page

  • 20555

end page

  • 20561

volume

  • 110

issue

  • 41