Why Is the C-terminus of A(1-42) More Unfolded than That of A<img src="http://pubs.acs.org/images/gifchars/beta2.gif"
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- 作者：Liang Shen ; Hong-Fang Ji ; Hong-Yu Zhang
- 刊名：Journal of Physical Chemistry B
- 出版年：2008
- 出版时间：March 13, 2008
- 年：2008
- 卷：112
- 期：10
- 页码：3164 - 3167
- 全文大小：244K
- 年卷期：v.112,no.10(March 13, 2008)
- ISSN：1520-5207
文摘
A<IMG SRC="/images/gifchars/beta2.gif" BORDER=0 ALIGN="middle">(1-40) and A
(1-42) are the main forms of amyloid (A) peptides in the brain of Alzheimer's patients;however, the latter possesses much stronger aggregation and deposition propensity than the former, which ispartially attributed to the more unfolded C-terminus of A(1-42) than that of A(1-40). To explore thephysical basis underlying the different dynamic behaviors of both A peptides, parallel molecular dynamics(MD) simulations on A(1-40) and A(1-42) were performed to investigate their thermal unfolding processes.It is revealed that the addition of residues 41 and 42 in A(1-42) disrupts the C-terminal hydrophobic core,which triggers the unraveling of the C-terminal helix of A(1-42). This conclusion is supported by the MDsimulation on the I41A mutant of A(1-42), in which the C-terminal helix possesses relatively higherconformational stability than that of wild type A(1-42) owing to the change in hydrophobic interactionpatterns.
(1-42) are the main forms of amyloid (A) peptides in the brain of Alzheimer's patients;however, the latter possesses much stronger aggregation and deposition propensity than the former, which ispartially attributed to the more unfolded C-terminus of A(1-42) than that of A(1-40). To explore thephysical basis underlying the different dynamic behaviors of both A peptides, parallel molecular dynamics(MD) simulations on A(1-40) and A(1-42) were performed to investigate their thermal unfolding processes.It is revealed that the addition of residues 41 and 42 in A(1-42) disrupts the C-terminal hydrophobic core,which triggers the unraveling of the C-terminal helix of A(1-42). This conclusion is supported by the MDsimulation on the I41A mutant of A(1-42), in which the C-terminal helix possesses relatively higherconformational stability than that of wild type A(1-42) owing to the change in hydrophobic interactionpatterns.