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Stanford's goal: to understand protein folding, protein aggregation, and related diseases.



What are proteins and why do they "fold"? Proteins are biology's workhorses -- its "nanomachines." Before proteins can carry out their biochemical function, they remarkably assemble themselves, or "fold." The process of protein folding, while critical and fundamental to virtually all of biology, remains a mystery. Moreover, perhaps not surprisingly, when proteins do not fold correctly (i.e. "misfold"), there can be serious effects, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), CJD, ALS, and Parkinson's disease.

What does Folding@Home do? Folding@Home is a distributed computing project which studies protein folding, misfolding, aggregation, and related diseases. Stanford uses novel computational methods and large scale distributed computing, to simulate timescales thousands to millions of times longer than previously achieved. This has allowed us to simulate folding for the first time, and to now direct Stanford's approach to examine folding related disease.



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 verlyol_[belgium]:09/24/14 
Study examines medical professional liability claims related to esophageal cancer screening
Many patients lack information about the use of targeted therapies, oncologists say
Significant presence of women in oncology, but still under-representation in leadership positions, Greek survey shows
What are the top 10 leading causes of death in the US?
Potent new cancer drugs likely with new protein 'map'
Survey reveals emotional exhaustion affects many cancer specialists
New estrogen-related breast cancer mechanism detected
Cancer during pregnancy: chemotherapy and radiotherapy are safe for babies, studies show
Anamorelin shown to improve appetite and body mass in patients with cancer anorexia-cachexia
Second-line afatinib significantly improves progression-free survival in recurrent or metastatic head and neck cancer, phase III trial shows
Rolapitant reduces nausea and vomiting in phase III trial
Strategy to reduce side effects in modern cancer therapy
Taller people at reduced risk of esophageal cancer
Genetic 'instruction set' for antibodies knocks down hepatitis C in mice
Scientists shed light on how to block protein that causes cancer, Alzheimer's
New approach offers hope for patients with autoimmune diseases, bone loss
With some tinkering, anthrax becomes an efficient drug carrier for cancer
Newly discovered marker may lead to early detection of pancreatic cancer
A vitamin D-derivative makes pancreatic tumors vulnerable to chemotherapy
Cancer metastatis may be stopped in its tracks with the help of bacterial "communication system"
Research uncovers tumors self-protection mechanism
UCLA scientists unlock protein that can accelerate recovery in cancer patients following radiation and chemotherapy
Simple blood test could be used as tool for early cancer diagnosis
Discrepancies in access to new cancer drugs revealed
False-positives tolerated to achieve diagnostic sensitivity
Remote healthcare for an aging population
Promising Alzheimer's treatment being tested by NeuroEM Therapeutics
Scientists shed light on how to block protein that causes cancer, Alzheimer's
Regeneration of brain stem cells boosted by turmeric compound
The emotion lingers long after the memories have vanished in Alzheimer's patients
Promising drug candidate for Alzheimer's found in turmeric compound
Viewing drugs' effect on living brain now possible with first mouse model for ALS dementia
New 'designer proteins' created in fight against Alzheimer's and cancer
Online resource encourages everyone to improve brain health
Memory complaints could be early indicator of future dementia risk
UK-based chemists report 'designer proteins' breakthrough
Cognitively demanding visual motor task can identify those at high risk for Alzheimer's disease
Down syndrome helps researchers understand Alzheimer's disease
Impaired brain signaling pathway 'may be a cause of Alzheimer's'
World Alzheimer Report 2014: the key points
UB researchers corroborate the neuroprotective effects of Sirtuin 1 activation on mice with Alzheimer's disease
Concussion-related brain disease identified in living brain
Sedentary behavior 'may counteract brain benefits of exercise in older adults'
Dementia risk reduction through tobacco control and better prevention, detection and control of hypertension and diabetes
Measuring modified protein structures
The cell recognizes the buildup of misfolded proteins, offers insight into Alzheimer's, ALS, Huntington's, Parkinson's, and type 2 diabetes
Brain may 'work around' early Alzheimer's damage
The young brains of city dwellers harmed by air pollution
Discovery may lead to improved memory, cognitive function in Alzheimer's patients
In mouse model of Alzheimer's disease, targeted immune booster removes toxic proteins
Study shows how chimpanzees share skills
Antibiotic exposure associated with early childhood obesity
Customising chemotherapy in lung cancer
Malaria severity influenced by five human genes, say researchers
Scientists shed light on how to block protein that causes cancer, Alzheimer's
Newly discovered marker may lead to early detection of pancreatic cancer
Research uncovers tumors self-protection mechanism
Magnetic field opens and closes nanovesicle
Protein controlling gut's protective force field identified: Immune-system receptor encourages growth of bacterial shield during illness
More evidence that Neanderthals and modern humans overlapped
Diabetes study: investigating fluctuations in blood sugar
Western University researchers explain the highs and lows of marijuana use
UK-based chemists report 'designer proteins' breakthrough
An old drug yields a potential new class of antibiotics
Mechanism of Parkinson's spread demonstrated
Healthy humans 'harbor an average of five viruses'
Pupil size shows reliability of decisions
Endocrine-related protein found to be master regulator in other important diseases
How do I smell? Much the same as how you see
Ebola virus protein offers potential drug target
Glaucoma cure may lie in targeting 'stiff cells' that impede fluid drainage
Is the pattern of brain folding a "fingerprint" for schizophrenia?
Scientists reset human stem cells in 'significant milestone' in medicine
Deactivating a cell protein may halt progress of rheumatoid arthritis
Gene 'may slow aging of entire body when activated in key organs'
  • Stickies: 0
  • News Articles: 159
  • Pages: 32
FahCore_11 has reached end of life
King_N
[H]ard|Folding Administrator


Posts: 104
Points: 2,859,398
Work Units: 6,705

Posted: Sun Sep 28, 2014 06:00 am
FahCore_11 has reached end of life
by Vijay Pande

Quote:
FahCore_11 WUs have been out of supply for some time now. We have been working to see if there are scientific problems which would be well suited by this core, but the science has moved on (FahCore_11 is very, very old and does not support key new advances) and, as mentioned earlier, it is time to retire FahCore_11.


Full Article: here.



A discussion of recent FAH work on protein aggregation-related diseases
by Jingcheng Wu

Quote:
For newly synthesized proteins to become functional, they have to fold into a particular three-dimensional structure or conformation first. During the folding process, a protein goes through a sequence of intermediate states to reach the final functional conformation or the native state. Unfortunately, protein folding isnt fail-proof. Sometimes, proteins misfold and become stuck in certain stable intermediate states without further proceeding to fold into their native states. Such misfolded proteins may aggregate and damage surrounding tissues.

Protein misfolding is implicated in a wide variety of diseases, including Alzheimers that affects about half of the population over 85 years of age (1), ALS that claimed the life of the legendary baseball player Lou Gehrig just before his 38th birthday (and leads to all of the recent ALS ice bucket challenges), Mad Cow Disease from eating contaminated beef that leads to spongy lesions in human brains. These diseases manifest different signs and symptoms based on varying factors. Such factors can be the type of misfolded protein and the location in organs that protein aggregation occurs. Some such diseases are limited to one specific organ, some spread to multiple organs; some are inherited, some are acquired; some have known causes, some happen without warnings; some mainly affect certain age groups, some span across generations.


Full Article: here.

Folding@home highlighted in Biophysical Journal
King_N
[H]ard|Folding Administrator


Posts: 104
Points: 2,859,398
Work Units: 6,705

Posted: Wed Aug 27, 2014 12:46 pm
Recent work from Folding@home highlighted in Biophysical Journal

Quote:
by Vijay Pande

Our recent work on understanding how protein misfolding occurs (http://www.cell.com/biophysj/abstract/S0006-3495(14)00722-X) has shed light on the nature of misfolding and potential subsequent aggregation (relevant for protein misfolding disease), demonstrating that misfolded states are more prevalent than would be expected, especially due to their metastability (once you get into a misfolded state, its really hard to get out of it).



Full Article: here.


New results for Opa proteins

Quote:
by Peter Kasson

Were excited to share some recent results from our lab that combine simulation and experimental structural biology. This has been a wonderful collaboration with my colleague Linda Columbus, a Chemistry professor at the University of Virginia. We are interested in how Neisseria bacteria recognize and infect cells. This is an important problem #1 because Neisseria are becoming increasingly drug-resistance and #2 because these mechanisms can be borrowed for targeted drug delivery.


Full Article: here.

Folding/Chrome to Reveal the Secrets Behind the Type II Diabetes
King_N
[H]ard|Folding Administrator


Posts: 104
Points: 2,859,398
Work Units: 6,705

Posted: Thu Jul 24, 2014 03:33 am
Quote:
by Huang

In the past couple of years, Xuhui Huangs group at HKUST
(http://compbio.ust.hk/) has performed large-scale molecular dynamics
simulations at Folding@Home (Project 2974-2975) to investigate the
mis-folding of the hIAPP (human islet amyloid polypeptide, also called
amylin).

Like other misfolding peptides, hIAPP is generally unstructured in
water solution but adopts an alpha-helix structure when binds to the
cellular membrane. Around 95% of patients with Type II diabetes
exhibit large deposits of misfolded hIAPP (beta-sheet fibrils). The
aggregation of this peptide is suggested to induce apoptotic
cell-death in insulin-producing β-cells that may further cause the
development of the type II diabetes. Using Markov state models
constructed from many molecular dynamics simulations, we have
identified the metastable conformational states of the hIAPP monomer
and the dynamics of transitioning between them. We show that even
though the overall structure of the hIAPP peptide lacks a dominant
folded structure, there exist a large number of reasonably populated
metastable conformational states. Among them, a few states containing
substantial amounts of β-hairpin secondary structure and extended
hydrophobic surfaces may further induce the nucleation of hIAPP
aggregation and eventually form the fibrils. These results were
published at Qin, Bowman, and Huang, J. Am. Chem. Soc., 135 (43),
1609216101, (2013) (http://pubs.acs.org/doi/full/10.1021/ja403147m).



Full Article: here.
Update on drug design successes with Folding@home
King_N
[H]ard|Folding Administrator


Posts: 104
Points: 2,859,398
Work Units: 6,705

Posted: Sat Jun 28, 2014 08:53 am
Vijay gave a brief talk on drug design successes with Folding@home.

Quote:
by Vijay Pande

In the Stanford Big Data conference in 2014, I gave a talk which gives an update on our drug design efforts, summarizing a bit on how FAH works to design drugs and were we are in some areas (but not all alas, its only a 12 minute talk, so I had to be pretty brief).



Link to video here.
Stanford Webinar
King_N
[H]ard|Folding Administrator


Posts: 104
Points: 2,859,398
Work Units: 6,705

Posted: Mon May 26, 2014 03:11 am
Stanford is holding a "Webinar".

Quote:
by Vijay Pande

Please join us on June 3rd for a webinar presented by Vijay Pande, Professor of Chemistry, Structural Biology, and Computer Science at Stanford University and the founder of the Folding@Home project. Professor Pande will give a brief introduction to Folding@home and successes in the project so far. He will also discuss plans to greatly enhance Folding@home capabilities through new initiatives.


The webinar is scheduled to take place on June 3rd at 9am, it requires registration at the link below.

Registration Link

  • Stickies: 0
  • News Articles: 159
  • Pages: 32
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