title: Predicting unfolding thermodynamics and stable intermediates for alanine-rich helical peptides with the aid of coarse-grained molecular simulation.
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.
authors.affiliation: Chemical & Biomolecular Engineering Department, University of Delaware, Newark, DE 19716, United States.
authors.forename: Cesar
authors.initials: C
authors.lastname: Calero-Rubio
authors.affiliation: Material Science & Engineering Department, University of Delaware, Newark, DE 19716, United States.
authors.forename: Bradford
authors.initials: B
authors.lastname: Paik
authors.affiliation: Material Science & Engineering Department, University of Delaware, Newark, DE 19716, United States.
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
authors.affiliation: Material Science & Engineering Department, University of Delaware, Newark, DE 19716, United States. Electronic address: kiick@udel.edu.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Kiick
authors.affiliation: Chemical & Biomolecular Engineering Department, University of Delaware, Newark, DE 19716, United States. Electronic address: cjr@udel.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D000409:Alanine / Q000737:chemistry*; D002942:Circular Dichroism; D003198:Computer Simulation; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D011489:Protein Denaturation; D013696:Temperature; D013816:Thermodynamics
chemical_list: D010455:Peptides; D000409:Alanine
keywords: Coarse-grained modeling; Conformational stability; Helical peptides; Molecular dynamics; Protein unfolding; Replica exchange