Ab initio folding of extended α‐helix: A theoretical study about the role of electrostatic polarization in the folding of helical structures

Abstract

In this work, we report the ab initio folding of three different extended helical peptides namely 2khk, N36, and C34 through conventional molecular dynamics simulation at room temperature using implicit solvation model. Employing adaptive hydrogen bond specific charge (AHBC) scheme to account for the polarization effect of hydrogen bonds established during the simulation, the effective folding of the three extended helices were observed with best backbone RMSDs in comparison to the experimental structures over the helical region determined to be 1.30 Å for 2khk, 0.73 Å for N36 and 0.72 Å for C34. In this study, 2khk will be used as a benchmark case serving as a means to compare the ability of polarized (AHBC) and nonpolarized force field in the folding of an extended helix. Analyses conducted revealed the ability of the AHBC scheme in effectively folding the extended helix by promoting helix growth through the stabilization of backbone hydrogen bonds upon formation during the folding process. Similar observations were also noted when AHBC scheme was employed during the folding of C34 and N36. However, under Amber03 force field, helical structures formed during the folding of 2khk was not accompanied by stabilization thus highlighting the importance of electrostatic polarization in the folding of helical structures.

Biomimetic Peptide Nanowires Designed for Conductivity

“…It is possible that the favored interactions between the aromatic amino acids of side chains exceed the interaction of backbone hydrogen bonds, which results in the bending of the extended helix. This finding is similar to the folding simulation of long proteins reported by Lazim et al and Duan et al To be clear, L6 was seen by contrast to adopt a stable α-helix conformation, in agreement with the CD data (Figure ). As F6 displays a less stable helix, it is less likely to form perfect coiled-coil structuresas evidenced by the experimental results, seen in the form of multiple fibril polymorphisms and imperfect CD curves.…”

Effects of Polarizable Solvent Models upon the Relative Stability of an α-Helical and a β-Hairpin Structure of an Alanine Decapeptide

“…It was concluded that the introduction of electronic polarizability into the solvent model appears of importance to a proper description of folding equilibria if these are determined by competing solute conformations that have different dipole moments. Other studies in the literature focused on the effect of including polarizability into the peptide model on the secondary structure of the solute − or the stability of the native protein fold. , …”