Systematic Examination of Polymorphism in Amyloid Fibrils by Molecular-Dynamics Simulation

Berryman, Joshua T.; Radford, Sheena E.; Harris, Sarah A.

doi:10.1016/j.bpj.2011.02.060

Cited by 46 publications

(54 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is shown in Figure 4d that for co-phe structure, the single point mutation significantly increases OP from ∼0.15 to ∼0.6. For aa-pho structure, the mutation increases OP from ∼0.35 to ∼0.4, which is much larger than ∼0.07, an indicative of thermodynamic instability [30]. In addition, the genetic mutation increases the OP of co-pho structures by the amount of ∼0.2.…”

Section: Resultsmentioning

confidence: 92%

See 1 more Smart Citation

Role of Sequence and Structural Polymorphism on the Mechanical Properties of Amyloid Fibrils

et al. 2014

View full text Add to dashboard Cite

Amyloid fibrils playing a critical role in disease expression, have recently been found to exhibit the excellent mechanical properties such as elastic modulus in the order of 10 GPa, which is comparable to that of other mechanical proteins such as microtubule, actin filament, and spider silk. These remarkable mechanical properties of amyloid fibrils are correlated with their functional role in disease expression. This suggests the importance in understanding how these excellent mechanical properties are originated through self-assembly process that may depend on the amino acid sequence. However, the sequence-structure-property relationship of amyloid fibrils has not been fully understood yet. In this work, we characterize the mechanical properties of human islet amyloid polypeptide (hIAPP) fibrils with respect to their molecular structures as well as their amino acid sequence by using all-atom explicit water molecular dynamics (MD) simulation. The simulation result suggests that the remarkable bending rigidity of amyloid fibrils can be achieved through a specific self-aggregation pattern such as antiparallel stacking of β strands (peptide chain). Moreover, we have shown that a single point mutation of hIAPP chain constituting a hIAPP fibril significantly affects the thermodynamic stability of hIAPP fibril formed by parallel stacking of peptide chain, and that a single point mutation results in a significant change in the bending rigidity of hIAPP fibrils formed by antiparallel stacking of β strands. This clearly elucidates the role of amino acid sequence on not only the equilibrium conformations of amyloid fibrils but also their mechanical properties. Our study sheds light on sequence-structure-property relationships of amyloid fibrils, which suggests that the mechanical properties of amyloid fibrils are encoded in their sequence-dependent molecular architecture.

show abstract

Section: Resultsmentioning

confidence: 92%

“…The structural stability of amyloid fibril is checked based on OP such that a fibril structure with its OP larger than 0.07 is regarded as an unstable and disordered structure [30].…”

Section: Methodsmentioning

confidence: 99%

Role of Sequence and Structural Polymorphism on the Mechanical Properties of Amyloid Fibrils

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It meanst hat the structural stability of heterogeneousf ibrils implies that the binding energy between blocks has ag reat effect. Understanding the mechanical properties of amyloid fibrils is important because they are highly relatedr epetitive fragmentation and elongation mechanisms [84,[95][96][97] and distorting cell membrane. The variations in binding energies showedd ifferent trends depending on the fibril composition.…”

Section: Bindingenergies and Root Mean Squared Fluctuation (Rmsf)mentioning

confidence: 99%

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

et al. 2017

View full text Add to dashboard Cite

In biological systems, structural confinements of amyloid fibrils can be mediated by the role of water molecules. However, the underlying effect of the dynamic behavior of water molecules on structural stabilities of amyloid fibrils is still unclear. By performing molecular dynamics simulations, we investigate the dynamic features and the effect of interior water molecules on conformations and mechanical characteristics of various amyloid fibrils. We find that a specific mechanism induced by the dynamic properties of interior water molecules can affect diffusion of water molecules inside amyloid fibrils, inducing their different structural stabilities. The conformation of amyloid fibrils induced by interior water molecules show the fibrils' different mechanical features. We elucidate the role of confined and movable interior water molecules in structural stabilities of various amyloid fibrils. Our results offer insights not only in further understanding of mechanical features of amyloids as mediated by water molecules, but also in the fine-tuning of the functional abilities of amyloid fibrils for applications.

show abstract

“…S2(c)]. Amyloids that have twist angle with OP values larger than 0.07 are considered to have disordered protein structures and increased thermodynamic stability with relatively low stability . Regardless of F20L mutation effects and polymorphic compositions, polymorphic F20L and WT Aβ pair oligomers' OP values occupied below 0.07 as shown in Supporting Information Figure S2(c).…”

Section: Resultsmentioning

confidence: 99%

Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations

et al. 2017

View full text Add to dashboard Cite

Aβ amyloid proteins are involved in neuro-degenerative diseases such as Alzheimer's, Parkinson's, and so forth. Because of its structurally stable feature under physiological conditions, Aβ amyloid protein disrupts the normal cell function. Because of these concerns, understanding the structural feature of Aβ amyloid protein in detail is crucial. There have been some efforts on lowering the structural stabilities of Aβ amyloid fibrils by decreasing the aromatic residues characteristic and hydrophobic effect. Yet, there is a lack of understanding of Aβ amyloid pair structures considering those effects. In this study, we provide the structural characteristics of wildtype (WT) and phenylalanine residue mutation to leucine (F20L) Aβ amyloid pair structures using molecular dynamics simulation in detail. We also considered the polymorphic feature of F20L and WT Aβ pair amyloids based on the facing β-strand directions between the amyloid pairs. As a result, we were able to observe the varying effects of mutation, polymorphism, and protofibril lengths on the structural stability of pair amyloids. Furthermore, we have also found that opposite structural stability exists on a certain polymorphic Aβ pair amyloids depending on its oligomeric or protofibrillar state, which can be helpful for understanding the amyloid growth mechanism via repetitive fragmentation and elongation mechanism. Proteins 2017; 85:580-592. © 2016 Wiley Periodicals, Inc.

show abstract

Systematic Examination of Polymorphism in Amyloid Fibrils by Molecular-Dynamics Simulation

Cited by 46 publications

References 54 publications

Role of Sequence and Structural Polymorphism on the Mechanical Properties of Amyloid Fibrils

Role of Sequence and Structural Polymorphism on the Mechanical Properties of Amyloid Fibrils

Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules

Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations

Contact Info

Product

Resources

About