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Primeur weekly 2014-02-24

Special

H2020: the long road to an integrated open and accessible European e-Infrastructure ...

PRACE, HPC applications and technological development: three ingredients for a top European strategy ...

Yannick Legré is the new director of EGI.eu ...

The Cloud

Red Hat Enteprise Linux OpenStack Platform leveraged by Alcatel-Lucent, CloudBand as part of its Network Functions Virtualization (NFV) Platform ...

AT&T and IBM join forces to deliver new innovations for the Internet of Things ...

Mellanox introduces CloudX Platform to enable companies to build the most efficient public, private and hybrid Clouds ...

EuroFlash

Powerful supercomputer to offer a glimpse of the early universe ...

From a distance: New technique for repair work ...

ECRIN-ERIC to host inauguration ceremony ...

Karlsruhe Institute of Technology to develop ultra-small and ultra–fast electro-optic modulator ...

SURFsara to host Data & Computing Infrastructure Event on 12-13 March 2014 ...

USFlash

SDSC team develops multi-scale simulation software for chemistry research ...

SDSC/UC San Diego researchers hone in on Alzheimer's disease ...

Intel advances next phase of Big Data intelligence: real time analytics ...

Supercomputer dramatically accelerates rapid genome analysis ...

Using computers to speed up drug discovery ...

Better cache management could improve chip performance and cut energy use ...

A step closer to a photonic future ...

HP delivers record-breaking performance and dramatic efficiencies with HP ProLiant servers ...

Researchers propose a better way to make sense of 'Big Data' ...

Mega-bucks from Russia seed development of 'Big Data' tools ...

A new laser for a faster Internet ...

C-DAC to organize Accelerating Biology 2014: Computing Life ...

NetApp introduces unified scale-out storage systems and virtualization software for the unbound Cloud era ...

Supermicro shipping 96 DIMM 4U 4-Way SuperServer featuring new Intel Xeon processor E7-8800/4800 v2 ...

SDSC/UC San Diego researchers hone in on Alzheimer's disease


14 Feb 2014 San Diego - Researchers studying peptides using the Gordon supercomputer at the San Diego Supercomputer Center (SDSC) at the University of California, San Diego have found new ways to elucidate the creation of the toxic oligomers associated with Alzheimer's disease.

Igor Tsigelny, a research scientist with SDSC, the UCSD Moores Cancer Center, and the Department of Neurosciences, focused on the small peptide called amyloid-beta, which pairs up with itself to form dimers and oligomers.

The scientists surveyed all the possible ways to look at the dynamics of conformational changes of these peptides and the possibility that they might organize into the oligomers theorized to be responsible for the degenerative brain disease. In the February 14 issue of theJournal of Alzheimer's Disease, the researchers suggest their results may generate new targets for drug development.

"Our research has identified amino acids for point mutations that either enhanced or suppressed the formation and toxicity of oligomer rings", stated Igor Tsigelny, the study's lead author. "Aggregation of misfolded neuronal proteins and peptides may play a primary role in neurodegenerative disorders, including Alzheimer's disease."

Igor Tsigelny also noted that recent improvements in computational processing speed have allowed him and other researchers to use a variety of tools, including computer simulations, to take new approaches to examining amyloid-beta, which has proven too unstable for traditional approaches such as x-ray crystallography.

The researchers investigated the single and dimer forms of the peptide with a combination of computational methods including molecular dynamics, molecular docking, molecular interactions with the membrane, as well as mutagenesis, biochemical, and electron microscopy studies. They then looked at how those dimers interacted with additional peptides and which larger structures resulted. The researchers found that depending on their configurations, some dimers did not lead to any further oligomerization and some form toxic oligomers implicated in the development of Alzheimer's disease.

"Remarkably, we showed a greater diversity in amyloid-beta dimers than previously described", stated Eliezer Masliah, professor of pathology and medicine at UC San Diego, and a member of the research team. "Understanding the structure of amyloid-beta dimers might be important for the design of small molecules that block formation of toxic oligomers."

Based on their results, the researchers were able to identify key amino acids that altered the formation and toxicity of oligomer rings. "Our data is only theoretical, but there is a good chance the oligomers we have been modelling exist for real", noted Eliezer Masliah. "Some important recent publications have come out that support our work."

The in silico experiments allowed the single amyloid-beta monomers to associate randomly, according to Eliezer Masliah. However, he noted that within the brains of Alzheimer's patients, the formation of oligomers and fibrils depends on any number of biochemical influences such as peptide concentration, oxidation, neurotoxins, and acidity.

According to the researchers, their work implicates a more dynamic role for the amyloid-beta dimers than previously thought. It also suggests that the way dimers form and then grow into larger structures is a rapidly changing process.

"This, as well as previous results, suggests that targeting selected amyloid-beta dimers may be important in an effort to ameliorate the episodic memory described in mild cognitive impairment and the early stages of Alzheimer's disease", stated Eliezer Masliah.

Eliezer Masliah and Igor Tsigelny's collaborators included UC San Diego's Yuriy Sharikov, Valentina Kouznetsova, Jerry Greenberg, Wolfgang Wrasidlo, Tania Gonzalez, Paula Desplats, Sarah E. Michael, Margarita Trejo-Morales, and Cassia Overk.
Source: San Diego Supercomputer Center - SDSC

Back to Table of contents

Primeur weekly 2014-02-24

Special

H2020: the long road to an integrated open and accessible European e-Infrastructure ...

PRACE, HPC applications and technological development: three ingredients for a top European strategy ...

Yannick Legré is the new director of EGI.eu ...

The Cloud

Red Hat Enteprise Linux OpenStack Platform leveraged by Alcatel-Lucent, CloudBand as part of its Network Functions Virtualization (NFV) Platform ...

AT&T and IBM join forces to deliver new innovations for the Internet of Things ...

Mellanox introduces CloudX Platform to enable companies to build the most efficient public, private and hybrid Clouds ...

EuroFlash

Powerful supercomputer to offer a glimpse of the early universe ...

From a distance: New technique for repair work ...

ECRIN-ERIC to host inauguration ceremony ...

Karlsruhe Institute of Technology to develop ultra-small and ultra–fast electro-optic modulator ...

SURFsara to host Data & Computing Infrastructure Event on 12-13 March 2014 ...

USFlash

SDSC team develops multi-scale simulation software for chemistry research ...

SDSC/UC San Diego researchers hone in on Alzheimer's disease ...

Intel advances next phase of Big Data intelligence: real time analytics ...

Supercomputer dramatically accelerates rapid genome analysis ...

Using computers to speed up drug discovery ...

Better cache management could improve chip performance and cut energy use ...

A step closer to a photonic future ...

HP delivers record-breaking performance and dramatic efficiencies with HP ProLiant servers ...

Researchers propose a better way to make sense of 'Big Data' ...

Mega-bucks from Russia seed development of 'Big Data' tools ...

A new laser for a faster Internet ...

C-DAC to organize Accelerating Biology 2014: Computing Life ...

NetApp introduces unified scale-out storage systems and virtualization software for the unbound Cloud era ...

Supermicro shipping 96 DIMM 4U 4-Way SuperServer featuring new Intel Xeon processor E7-8800/4800 v2 ...