Examination of the Effect of N‐terminal Diproline and Charged Side Chains on the Stabilization of Helical Conformation in Alanine–based Short Peptides: A Molecular Dynamics Study

The effect of N‐terminal diproline segment and charged side chains on the stabilization of helical conformation in alanine‐based short peptides are examined using molecular dynamics (MD) simulations. The cationic peptides, Ac–Pro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (Ia) and Ac–DPro1–Pro2–Ala3–Lys4–Ala5–Lys6–Ala7–Lys8–Ala9–NH2 (IIa) are examined for the role of lysine side chains on the inducement of helical conformation in alanine‐based short peptides. To examine the influence of lysine and glutamic acid in the i, i + 4 arrangement on the stabilization of helical conformation, cationic peptides, Ia and IIa, are modified as ion‐pair peptides, Ac–Pro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (Ib) and Ac–DPro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (IIb), respectively. MD simulations manifest enhanced occupancies in the α basin of ϕ, ψ space for ion‐pair peptides as compare to cationic peptides. The radial distribution function (RDF) analysis highlight that large side chain substituents of lysine and glutamic acid assist in helix formation by blocking water molecules from solvating backbone CO and NH groups.N‐terminal diproline of homochiral structure, LPro–LPro, and large side chain substituents of lysine and glutamic acid residues in the i, i + 4 arrangement stabilize the helical conformation in alanine‐based nonapeptide, Ac–Pro1–Pro2–Glu3–Glu4–Ala5–Ala6–Lys7–Lys8–Ala9–NH2 (Ib), as observed in the second most‐populated microstate, m2, during molecular dynamics in explicit‐water.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135318/1/slct201601381-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135318/2/slct201601381_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135318/3/slct201601381.pd