The Mantid framework is a software solution developed for the analysis and visualization of neutron scattering and muon spin measurements. The framework is jointly developed by software engineers and scientists at the ISIS Neutron and Muon Facility and the Oak Ridge National Laboratory. The objectives, functionality and novel design aspects of Mantid are described.

The aggregation of alpha-helix-rich proteins into beta-sheet-rich amyloid fibrils is associated with fatal diseases, such as Alzheimer's disease and prion disease. During an aggregation process, protein secondary structure elements-alpha-helices-undergo conformational changes to beta-sheets. The fact that proteins with different sequences and structures undergo a similar transition on aggregation suggests that the sequence nonspecific hydrogen bond interaction among protein backbones is an important factor. We perform molecular dynamics simulations of a polyalanine model, which is an alpha-helix in its native state and observe a metastable beta-hairpin intermediate. Although a beta-hairpin has larger potential energy than an alpha-helix, the entropy of a beta-hairpin is larger because of fewer constraints imposed by the hydrogen bonds. In the vicinity of the transition temperature, we observe the interconversion of the alpha-helix and beta-sheet states via a random coil state. We also study the effect of the environment by varying the relative strength of side-chain interactions for a designed peptide-an alpha-helix in its native state. For a certain range of side-chain interaction strengths, we find that the intermediate beta-hairpin state is destabilized and even disappears, suggesting an important role of the environment in the aggregation propensity of a peptide.

Experimental evidence suggests that the folding and aggregation of the amyloid ␤-protein (A␤) into oligomers is a key pathogenetic event in Alzheimer's disease. Inhibiting the pathologic folding and oligomerization of A␤ could be effective in the prevention and treatment of Alzheimer's disease. Here, using all-atom molecular dynamics simulations in explicit solvent, we probe the initial stages of folding of a decapeptide segment of A␤, A␤21-30, shown experimentally to nucleate the folding process. In addition, we examine the folding of a homologous decapeptide containing an amino acid substitution linked to hereditary cerebral hemorrhage with amyloidosis-Dutch type, [Gln-22]A␤ 21-30. We find that: (i) when the decapeptide is in water, hydrophobic interactions and transient salt bridges between Lys-28 and either Glu-22 or Asp-23 are important in the formation of a loop in the Val-24 -Lys-28 region of the wild-type decapeptide; (ii) in the presence of salt ions, salt bridges play a more prominent role in the stabilization of the loop; (iii) in water with a reduced density, the decapeptide forms a helix, indicating the sensitivity of folding to different aqueous environments; and (iv) the ''Dutch'' peptide in water, in contrast to the wild-type peptide, fails to form a long-lived Val-24 -Lys-28 loop, suggesting that loop stability is a critical factor in determining whether A␤ folds into pathologic structures. molecular dynamics ͉ Alzheimer's disease ͉ hydrophobic interactions ͉ salt bridges T he amyloid cascade hypothesis, first proposed in the early 1990s, posits that the deposition of amyloid fibrils is the seminal event in the pathogenesis of Alzheimer's disease (1, 2). However, recent biophysical, biological, and clinical data indicate that the formation of oligomeric assemblies much smaller than fibrils may be a key pathologic event (3-10). This paradigm shift suggests an attractive therapeutic approach: prevent or disrupt the assembly of amyloid ␤-protein (A␤) monomer into toxic oligomers. To do so requires an understanding of the molecular dynamics (MD) involved in the transition from nontoxic monomeric to toxic oligomeric states.Elucidation of the initial events in A␤ monomer folding and assembly is complicated by the solvent dependence of the process (11). Monomeric A␤ is largely helical in a membrane or membrane-mimicking environment such as ionic detergents (12-15). In contrast, A␤ monomers in aqueous solution show negligible ␣-helix or ␤-sheet content (11,16,17). Studies of A␤ 10 -35 -amide at micromolar concentrations in water show a pH-dependent folding transition in which the conformation is not helical but contains several turns and at least two short strands (18). Solution-state NMR combined with diffusionordered spectroscopy indicate that variation of the anionic strength in the buffer shifts the equilibrium between monomeric and oligomeric states, possibly allowing for the stabilization of intermediate structures (19). MD studies of A␤ 16 -22 monomer in aqueous urea solution show that increasin...