Title
Predicting unfolding thermodynamics and stable intermediates for alanine-rich helical peptides with the aid of coarse-grained molecular simulation
Author
Cesar Calero-Rubio, Bradford Paik, Xinqiao Jia, Kristi L. Kiick, Christopher J. Roberts
Year
2016
Journal
Biophysical Chemistry
Abstract
This report focuses on the molecular-level processes and thermodynamics of unfolding of a series of helical peptides using a coarse-grained (CG) molecular model. The CG model was refined to capture thermodynamics and structural changes as a function of temperature for a set of published peptide sequences. Circular dichroism spectroscopy (CD) was used to experimentally monitor the temperature-dependent conformational changes and stability of published peptides and new sequences introduced here. The model predictions were quantitatively or semi-quantitatively accurate in all cases. The simulations and CD results showed that, as expected, in most cases the unfolding of helical peptides is well described by a simply 2-state model, and conformational stability increased with increased length of the helices. A notable exception in a 19-residue helix was when two Ala residues were each replaced with Phe. This stabilized a partly unfolded intermediate state via hydrophobic contacts, and also promoted aggregates at higher peptide concentrations.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Protein folding, Thermal stability, Aggregation, Thermodynamics, Biochemistry