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Hydrogen sulfide concentration in the milieu of the hydrated alanine dipeptide determines its polyproline II‐beta propensity: Main chain contribution to the energetic origin of the formation of amyloid
Author(s) -
Mirkin Noemi G.,
Krimm Samuel
Publication year - 2020
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23356
Subject(s) - polyproline helix , chemistry , dipeptide , amyloid beta , peptide , context (archaeology) , ab initio , amyloid (mycology) , hydrogen sulfide , protein folding , stereochemistry , biochemistry , organic chemistry , sulfur , inorganic chemistry , paleontology , biology
In view of the observation that the concentration of hydrogen sulfide in brains with Alzheimer’s disease (AD) is lower than that in normal brains and in line with our previous studies indicating that additional content in the aqueous environment (milieu) of a peptide can change its local energetic preference from a polyproline II (P) to a β conformation (and therefore its tendency to form the β‐chain structures that lead to the amyloid plaques associated with the disease), we have studied the effect of H 2 S concentration on such propensity in a simple model peptide, the alanine dipeptide (ADP). The two concentration states are represented by ADP(H 2 O) 18 (H 2 S) and ADP(H 2 O) 18 (H 2 S) 2 . Ab initio calculations of these structures show that the lowest energy of the former is a β conformation while that of the latter is a P, mirroring the observed AD results and strengthening our proposal that amyloid diseases are better viewed in the context of a protein milieu‐folding paradigm.