NMR structure of the water soluble Aβ17–34 peptide

Fonar, Genadiy; Samson, Abraham O.

doi:10.1042/bsr20140094

Cited by 5 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is in agreement with a report based on a completely different simulation setup, where a similar intermediate with 3 10 -helical structure between residues 26 and 28 was sampled in Aβ21-30 41 . The final CPD-folded structure does not exhibit a well-defined α-helical structure prior to the kink (residues 19–26) (Fig 2B) but is within 3.42 Å (backbone RMSD) of the reference folded structure of Aβ17-34 (PDB ID 2MJ1) 40 . It is worth noting here that the reference folded structures from the NMR ensemble differ from one another by up to 2.79 Å.…”

Section: Resultsmentioning

confidence: 95%

“…It is worth noting here that the reference folded structures from the NMR ensemble differ from one another by up to 2.79 Å. Moreover, in the NMR experiment, the Aβ17-34 contained two additional glutamic acid residues at each terminus, which increased solubility and stabilized the helical structure in aqueous solution 40 ; since our simulations only included residues 17–34 (i.e., without the terminal residues added to stabilize the helix), we consider that CPD achieved a satisfactory proportion of helical structure.…”

Section: Resultsmentioning

confidence: 97%

“…The folding of the Aβ peptide and various Aβ segments has been the topic of intense study because of its association with the progression of Alzheimer’s disease 39 . The water soluble Aβ17-34 is an 18-residue (LVFFAEDVGSNKGAIIGL) segment of Aβ, which, in aqueous solutions under physiological conditions, was observed to adopt an α-helical structure for residues 19–26 and 28–33, with a kink around residues 26–28 (Fig 2B) 40 .…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Charge-perturbation dynamics — a new avenue towards in silico protein folding

Pant

Ramos

Ionescu

et al. 2019

Preprint

View full text Add to dashboard Cite

13Molecular dynamics (MD) has greatly contributed to understanding and predicting the way 14 proteins fold. However, the time-scale and complexity of folding are not accessible via 15 classical MD. Furthermore, efficient folding pipelines involving enhanced MD techniques 16 are not routinely accessible. We aimed to determine whether perturbing the electrostatic 17 component of the MD force field can help expedite folding simulations. We developed 18 charge-perturbation dynamics (CPD), an MD-based simulation approach that involves 19 periodically perturbing the atomic charges to values non-native to the MD force field. CPD 20 obtains suitable sampling via multiple iterations in which a classical MD segment (with 21 native charges) is followed by a very short segment of perturbed MD (using the same force 22 field and conditions, but with non-native charges); subsequently, partially folded 23 intermediates are refined via a longer segment of classical MD. Among the partially folded 24 structures from low-energy regions of the free-energy landscape sampled, the lowest-25 energy conformer with high root-mean-square deviation to the starting structure and low 26 radius of gyration is defined as the folded structure. Upon benchmark testing, we found 27 that medium-length peptides such as an alanine-based pentadecapeptide, an amyloid-β 28 peptide, and the tryptophan-cage mini-protein can fold starting from their extended linear 29 structure in under 45 ns of CPD (total simulation time), versus over 100 ns of classical 30 MD. CPD not only achieved folding close to the desired conformation but also sampled 31 key intermediates along the folding pathway without prior knowledge of the folding 32 mechanism or final folded structure. Our findings confirmed that perturbing the 33 electrostatic component of the classical MD force field can help expedite folding 34 3 simulations without changing the MD algorithm or using expensive computing 35 architectures. CPD can be employed to probe the folding dynamics of known, putative, or 36 planned peptides, as well as to improve sampling in more advanced simulations or to guide 37 further experiments. 38 39 4 Author summary 40 Folding represents the process by which proteins assemble into biologically active 41 conformations. While computational techniques such as molecular dynamics (MD) have 42 provided invaluable insight into protein folding, efficient folding pipelines are not 43 routinely accessible. In MD, the behavior of the studied molecule is simulated under the 44 concerted action of multiple forces described by mathematical functions employing 45 optimized parameters. Using non-native parameters effectively perturbs the MD force 46field. We show that this can be exploited to help expedite folding simulations. Specifically, 47we developed charge-perturbation dynamics (CPD), an MD-based simulation approach 48 that involves periodically perturbing the force field by using non-native atomic charges. 49For folding medium-length peptides such as the tryptophan-cage mini-protein s...

show abstract

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Charge-perturbation dynamics — a new avenue towards in silico protein folding

Pant

Ramos

Ionescu

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…It is pertinent to compare the structure of the aqueous A (25-35) peptide studied here to that of other amyloid peptides. Fonar and Samson (2014) demonstrated by NMR that A (17-34) in water solution adopts an -helical structure for the residues 19-26 and 28-33. Another study on a larger peptide, A (1-40) studied in aqueous environment at pH 7.3 using NMR spectroscopy (Vivekanandan et al, 2011) showed that the peptide adopts a stable -helical structure in the central hydrophobic core and contacts of the N-and C-termini with the central -helix.…”

Section: Discussionmentioning

confidence: 99%

Conformational Particularities of A(25-35) Peptide Determined by Infrared Spectroscopy

Najafova

2024

APR

View full text Add to dashboard Cite

The Alzheimer’s amyloid-β (25-35) peptide retains the toxicity and ability to aggregate of the amyloid-(1-40) peptide. The study of the conformational properties of Aβ (25-35) peptide in its soluble monomeric form can play an essential role in determining the mechanism of oligomerization. In this study, we probed the secondary structure of a soluble Aβ (25-35) peptide in water solution at physiological conditions (pH 7.4). We have used Fourier Transformed Infrared Spectroscopy (FTIR) to examine the secondary structure of this peptide. The amide I bands of A (25-35) obtained from transmission-FTIR spectra consists of one main band at 1658 cm-1, at both concentrations used (200 M and 1 mM). This band show us that A (25-35) in aqueous solution was mostly organized into a -helical structure (48%). The contribution of the unordered structure was found to be about 12%. The proportion of -sheet and -turn structures are slightly lower, 12-15% and 13-14%, respectively for both concentrations. FTIR spectra of the peptide in water solution (100 µM) after incubation for 12h showed Aβ peptide conformation is critically dependent on the environmental conditions used.

show abstract

Complexes Aβ(1–42) polypeptide with non-protein molecules

Banach

Roterman

2020

From Globular Proteins to Amyloids

View full text Add to dashboard Cite

NMR structure of the water soluble Aβ17–34 peptide

Cited by 5 publications

References 34 publications

Charge-perturbation dynamics — a new avenue towards in silico protein folding

Charge-perturbation dynamics — a new avenue towards in silico protein folding

Conformational Particularities of A(25-35) Peptide Determined by Infrared Spectroscopy

Complexes Aβ(1–42) polypeptide with non-protein molecules

Contact Info

Product

Resources

About