IMR Press / FBL / Volume 13 / Issue 10 / DOI: 10.2741/2983

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


In silico study on the effect of F19T mutation on amyloid-β peptide (10-35)

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1 Department of Chemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China
2 State Key Lab of Molecular Dynamics and Stable Structures, College of Chemistry, Peking University, Beijing, China

*Author to whom correspondence should be addressed.

Academic Editor: Buyong Ma

Front. Biosci. (Landmark Ed) 2008, 13(10), 3951–3965;
Published: 1 May 2008
(This article belongs to the Special Issue Computaional studies of protein aggregation)

The wild type (WT) amyloid-β (10-35) peptide, Aβ (10-35), and its F19T mutant have been studied by molecular dynamics simulations at 340 K in explicit water solvent each for over 3.4 µs. The WT peptide has a strong preference to form an E22-K28 loop (44% of total conformations) and a reasonable stability for a strand-loop-strand (SLS, L17-M35) (9%). The F19T mutant has a significantly lower population of E22-K28 loop (14%) and SLS structure (1.7%), but has a high population of Q15-D23 loop (48%). A specific interaction pattern among D23, V24, E22 and K28 was found to stabilize the E22-K28 loop in WT. Our results are in agreement with several experimental observations including: (1) the NOE constraints for the Aβ are reproduced; (2) the regions (15-23) and (22-28) can form loops; (3) the WT peptide is more structured than the F19T mutant. The current results also support our early proposal that the SLS structure might be important intermediate for monomer deposition to fibril, which explains the experimental fact that F19T mutant resists deposition to fibril.

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