An α-helix mimetic oligopyridylamide, ADH-31, modulates Aβ₄₂ monomer aggregation and destabilizes protofibril structures: insights from molecular dynamics simulations

Abstract

Alzheimer’s disease (AD) is a neurological disorder, growing epidemic across worldwide due to no effective medical aid available in the market. AD is known to be directly associated with toxicity...

Triazole–Peptide Conjugate as a Modulator of Aβ-Aggregation, Metal-Mediated Aβ-Aggregation, and Cytotoxicity

“…61 The conformational changes in the Aβ 42 monomer and protofibril structures in the absence and presence of DS2 were analyzed by the dictionary of the secondary structure of proteins method using gmx tool "do_dssp tool". 62 The J-coupling ( 3 J NH−Hα ) constants between the Hα proton and amide proton were evaluated as described previously 63 and compared with the experimental 3 J NH−Hα data. The binding free energy analysis was done according to our previous studies.…”

“…The binding free energy analysis was done according to our previous studies. 63 The binding free energy and per-residue binding free energy of DS2 with Aβ 42 monomer and protofibril structures were evaluated by the molecular mechanics Poisson−Boltzmann surface area (MM−PBSA) method using the "g_mmpbsa" tool. 64 ■ ASSOCIATED CONTENT * sı Supporting Information…”

“…The J -coupling ( 3 J NH–Hα ) constants between the Hα proton and amide proton were evaluated as described previously and compared with the experimental 3 J NH–Hα data. The binding free energy analysis was done according to our previous studies . The binding free energy and per-residue binding free energy of DS2 with Aβ 42 monomer and protofibril structures were evaluated by the molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) method using the “g_mmpbsa” tool …”

Mechanistic insights into the mitigation of Aβ aggregation and protofibril destabilization by ad-enantiomeric decapeptide rk10

“…Further, these values were compared with experimental chemical shifts of Ab 42 monomer reported by Hou et al 46 and Ab 42 protofibril taken from Biological Magnetic Resonance Data Bank (https://bmrb.io/data_library/summary/ ?bmrbId=27212, 5OQV's BMRB Entry = 27212). 47 The J-coupling ( 3 J NH-Ha ) constants between Ha proton of amino acid and amide proton in peptide were evaluated as described previously 48 and compared with the experimental 3 J NH-Ha data.…”

“…The PCA, FEL, and binding free energy analysis were done according to our previous studies. 48,49 The gmx utilities, ''gmx covar, and gmx sham'' were used to analyze the PCA and FEL. The binding free energy was calculated by GROMACS tool, ''gmx_mmpbsa''.…”