How can a β-sheet peptide be both a potent antimicrobial and harmfully toxic? Molecular dynamics simulations of protegrin-1 in micelles

Biopolymers ◽  
2006 ◽  
Vol 84 (2) ◽  
pp. 219-231 ◽  
Author(s):  
Allison A. Langham ◽  
Himanshu Khandelia ◽  
Yiannis N. Kaznessis
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations ◽  
Β Sheet

scholarly journals Structural Influence and Interactive Binding Behavior of Dopamine and Norepinephrine on the Greek-Key-Like Core of α-Synuclein Protofibril Revealed by Molecular Dynamics Simulations

Processes ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 850
Author(s):  
Yu Zou ◽  
Zhiwei Liu ◽  
Zhiqiang Zhu ◽  
Zhenyu Qian
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Therapeutic Strategy ◽  
Binding Capacity ◽  
Salt Bridges ◽  
Drug Candidates ◽  
Binding Behavior ◽  
Dynamics Simulations ◽  
Structural Influence ◽  
Β Sheet

The pathogenesis of Parkinson’s disease (PD) is closely associated with the aggregation of α-synuclein (αS) protein. Finding the effective inhibitors of αS aggregation has been considered as the primary therapeutic strategy for PD. Recent studies reported that two neurotransmitters, dopamine (DA) and norepinephrine (NE), can effectively inhibit αS aggregation and disrupt the preformed αS fibrils. However, the atomistic details of αS-DA/NE interaction remain unclear. Here, using molecular dynamics simulations, we investigated the binding behavior of DA/NE molecules and their structural influence on αS44–96 (Greek-key-like core of full length αS) protofibrillar tetramer. Our results showed that DA/NE molecules destabilize αS protofibrillar tetramer by disrupting the β-sheet structure and destroying the intra- and inter-peptide E46–K80 salt bridges, and they can also destroy the inter-chain backbone hydrogen bonds. Three binding sites were identified for both DA and NE molecules interacting with αS tetramer: T54–T72, Q79–A85, and F94–K96, and NE molecules had a stronger binding capacity to these sites than DA. The binding of DA/NE molecules to αS tetramer is dominantly driven by electrostatic and hydrogen bonding interactions. Through aromatic π-stacking, DA and NE molecules can bind to αS protofibril interactively. Our work reveals the detailed disruptive mechanism of protofibrillar αS oligomer by DA/NE molecules, which is helpful for the development of drug candidates against PD. Given that exercise as a stressor can stimulate DA/NE secretion and elevated levels of DA/NE could delay the progress of PD, this work also enhances our understanding of the biological mechanism by which exercise prevents and alleviates PD.

Molecular dynamics simulations of Aβ fibril interactions with β-sheet breaker peptides

Peptides ◽  
2010 ◽  
Vol 31 (11) ◽  
pp. 2100-2108 ◽  
Author(s):  
Neil J. Bruce ◽  
Deliang Chen ◽  
Shubhra G. Dastidar ◽  
Gabriel E. Marks ◽  
Catherine H. Schein ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations ◽  
Β Sheet

Molecular dynamics simulations reveal the mechanism of graphene oxide nanosheet inhibition of Aβ1–42 peptide aggregation

2019 ◽  
Vol 21 (21) ◽  
pp. 10981-10991 ◽  
Author(s):  
Yibo Jin ◽  
Yunxiang Sun ◽  
Yujie Chen ◽  
Jiangtao Lei ◽  
Guanghong Wei
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonding ◽  
Graphene Oxide ◽  
Molecular Dynamics Simulations ◽  
Salt Bridge ◽  
Graphene Oxide Nanosheets ◽  
Peptide Interactions ◽  
Graphene Oxide Nanosheet ◽  
Dynamics Simulations ◽  
Β Sheet

Graphene oxide nanosheets inhibit Aβ1–42 aggregation by weakening inter-peptide interactions and reducing β-sheet contents mostly via salt bridge, hydrogen bonding and cation–π interactions with charged residues.

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