%0 Book Section %1 statphys23_0910 %A Lam, A.R. %A Urbanc, B. %A Stanley, H.E. %B Abstract Book of the XXIII IUPAP International Conference on Statistical Physics %C Genova, Italy %D 2007 %E Pietronero, Luciano %E Loreto, Vittorio %E Zapperi, Stefano %K alzheimer amyloid discrete disease dynamics folding molecular protein statphys23 topic-10 %T In Silico Studies of Alzheimer $\beta$-protein A$\beta$ Folding %U http://st23.statphys23.org/webservices/abstract/preview_pop.php?ID_PAPER=910 %X Pathological folding and oligomerization of amyloid $\beta$-protein (A$\beta$) are widely perceived as central to Alzheimer's disease (AD). A$\beta$ exists in two alloforms, A$\beta$40 and A$\beta$42, of which A$\beta$42 is linked particularly strongly to AD. Here we apply a discrete molecular dynamics approach and a four-bead protein model with backbone hydrogen bonding and residue-specific effective hydropathic and electrostatic interactions (EIs) to study temperature dependence of A$\beta$40 and A$\beta$42 folding at different strengths of EIs. Our results show that at low temperatures both A$\beta$40 and A$\beta$42 monomers adopt a predominantly collapsed--coil conformation with a small $\alpha$-helical component. At higher temperatures, the $\beta$-strand structure becomes more prominent in both alloform. A$\beta$42 monomer conformation is characterized by a larger number of $\beta$-strands than A$\beta$40 conformation. The temperature dependence of the A$\beta$ folded structure is in a good agreement with recent experimental findings. At all temperatures, folded structures of A$\beta$40 and A$\beta$42 show differences in the N-terminal and C-terminal regions. The folded A$\beta$42 monomer has an additional turn structure at the C-terminus not present in A$\beta$40, consistent with recent in vitro findings. By varying the strength of EIs, we examine the A$\beta$40 and A$\beta$42 conformational changes due to a change in pH. At the highest strength of EIs, the folded structures of A$\beta$40 and A$\beta$42 have the highest amount of $\beta$-strand structure, while more globular conformations are observed at the lowest strength of EIs. Our results demonstrate that A$\beta$ folding is strongly sensitive to both temperature and pH variations, suggesting a possibility of different aggregation pathways at slightly different external conditions.

@incollection{statphys23_0910, abstract = {Pathological folding and oligomerization of amyloid $\beta$-protein (A$\beta$) are widely perceived as central to Alzheimer's disease (AD). A$\beta$ exists in two alloforms, A$\beta$40 and A$\beta$42, of which A$\beta$42 is linked particularly strongly to AD. Here we apply a discrete molecular dynamics approach and a four-bead protein model with backbone hydrogen bonding and residue-specific effective hydropathic and electrostatic interactions (EIs) to study temperature dependence of A$\beta$40 and A$\beta$42 folding at different strengths of EIs. Our results show that at low temperatures both A$\beta$40 and A$\beta$42 monomers adopt a predominantly collapsed--coil conformation with a small $\alpha$-helical component. At higher temperatures, the $\beta$-strand structure becomes more prominent in both alloform. A$\beta$42 monomer conformation is characterized by a larger number of $\beta$-strands than A$\beta$40 conformation. The temperature dependence of the A$\beta$ folded structure is in a good agreement with recent experimental findings. At all temperatures, folded structures of A$\beta$40 and A$\beta$42 show differences in the N-terminal and C-terminal regions. The folded A$\beta$42 monomer has an additional turn structure at the C-terminus not present in A$\beta$40, consistent with recent {\it in vitro} findings. By varying the strength of EIs, we examine the A$\beta$40 and A$\beta$42 conformational changes due to a change in pH. At the highest strength of EIs, the folded structures of A$\beta$40 and A$\beta$42 have the highest amount of $\beta$-strand structure, while more globular conformations are observed at the lowest strength of EIs. Our results demonstrate that A$\beta$ folding is strongly sensitive to both temperature and pH variations, suggesting a possibility of different aggregation pathways at slightly different external conditions.}, added-at = {2007-06-20T10:16:09.000+0200}, address = {Genova, Italy}, author = {Lam, A.R. and Urbanc, B. and Stanley, H.E.}, biburl = {https://www.bibsonomy.org/bibtex/2bdcb6d6c6d0f9475e9cac263a67b7b48/statphys23}, booktitle = {Abstract Book of the XXIII IUPAP International Conference on Statistical Physics}, editor = {Pietronero, Luciano and Loreto, Vittorio and Zapperi, Stefano}, interhash = {ec7b5b0dca74beab817ad3ed96ef8985}, intrahash = {bdcb6d6c6d0f9475e9cac263a67b7b48}, keywords = {alzheimer amyloid discrete disease dynamics folding molecular protein statphys23 topic-10}, month = {9-13 July}, timestamp = {2007-06-20T10:16:34.000+0200}, title = {{\bf In Silico} Studies of Alzheimer $\beta$-protein A$\beta$ Folding}, url = {http://st23.statphys23.org/webservices/abstract/preview_pop.php?ID_PAPER=910}, year = 2007 }