p2057_abeta_4mer
 

 

 Molecular features of APP and Ab peptides

 

 

 

Ab is a 40 to 43 amino-acid peptide
Ab deposits are in the grey matter of cortical areas
Ab 42 and 40 distribution in the aging brain
Ab 42 and 40 distribution in Alzheimer's disease
Tau pathology precedes Ab deposits in sporadic  AD
 Ab 42 and 40 deposition versus pathological tau stages
N-truncated Ab 42 species are the germs of amyloid
  Tau is upstream the amyloid cascade 
 Ab neurotoxicity
 Ab neurotoxicity
Ab clearance
Ab antibodies
 
APP cleavage for the production of Ab

Dysfunction of APP

 

 

 

p2057 points 159, days 31 

 

 

 

Projects 2051-2058

Followups for the 2000-2004 projects with different peptide length, environment and force fields. Furthermore the new implicit model gets tested (project 2054).

 

 

 

Projects 2000-2004

 

These are simulations with four Abeta chains, where the water is treated by different continuum approaches. Therefore these projects are very similar to the P722-724 systems. These project are designed to evaluate the implicit solvent models for the early steps of the aggregation process of the Abeta peptide. This is especially meant to be compared to the explicit results from the earlier projects.
Points and deadlines:
p2000 points 154, days 44; p2001 not released; p2002 points 180, days 51; p2003 points 162, days 46; p2004 not released

 

 

 

Projects 722-724

  

The aggregation of the Beta Amyloid peptide (Abeta, also known as Alzheimer's peptide) is thought to be responsible for nerve cell death in Alzheimer's Disease. Understanding what causes these peptides to aggregate could help scientists direct their search for possible drugs that can cure or at least relieve the symptoms of Alzheimers. 

 

 

 

 

 

These are tetramer simulations (picture above), simulating four Abeta chains in explicit water, studying how they come together and what the tetramer looks like. These are amongst the most demanding WUs so far because of the large system size. There have been some technical problems with the WU but with the help of the feedback from folders on beta, we have narrowed down the possible causes and hopefully P724 will not have any problems.