Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-42)

Tautomeric state of histidine is one of the factors that influence the structural and aggregation properties of amyloid beta (A beta)-peptide in neutral state. It is worth it to uncover the monomeric properties of A beta(1-42) peptide in comparison with A beta(1-40) peptide. Our replica-exchange molecular dynamics simulations results show that the sheet content of each tautomeric isomer in A beta(1-42) monomer is slightly higher than that in A beta(1-40) monomer except His6(delta)-His13(delta)-His14(delta) (delta delta delta) isomer, implying higher aggregation tendency in A beta(1-42), which is in agreement with previous experimental and theoretical studies. Further analysis indicates that (epsilon epsilon epsilon), (epsilon delta epsilon), (epsilon delta delta), and (delta delta epsilon) isomers prefer sheet conformation although they are in nondominating states. Particularly, it is confirmed that antiparallel beta-sheets of (epsilon delta delta) were formed at K16-E22 (22.0-43.9%), N27-A30 except G29 (21.9-40.2%), and M35-141 except G37 (24.1-43.4%). Furthermore, (eSO) may be the easiest one to overcome structural transformation due to nonobstructing interactions between K16 and/or L17 and histidine residues. The current study will help to understand the tautomeric effect of A beta(1-42) peptide to overcome Alzheimer's disease.