Abstract：
BACKGROUND: The importance of aromaticity vs. hydrophobicity of the central hydrophobic core (CHC, residues 17-20) in governing fibril formation in Aβ(1-42) has been the focus of an ongoing debate in the literature.
BACKGROUND: Mutations in the CHC (especially at Phe19 and Phe20) have been used to examine the relative impact of hydrophobicity and aromaticity on the degree of aggregation of Aβ(1-42). However, the results have not been conclusive.
METHODS: Partial least squares (PLS) modeling of aggregation rates, using reduced properties of a series of position 19 mutants, was employed to identify the physicochemical properties that had the greatest impact on the extent of aggregation.
RESULTS: The PLS models indicate that hydrophobicity at position 19 of Aβ(1-42) appears to be the primary and dominant factor in controlling Aβ(1-42) aggregation, with aromaticity having little effect.
CONCLUSIONS: This study illustrates the value of using reduced properties of amino acids in conjunction with PLS modeling to investigate mutational effects in peptides and proteins, as the reduced properties can capture in a quantitative manner the different physicochemical properties of the amino acid side chains. In this particular study, hydrophobicity at position 19 was determined to be the dominant property controlling aggregation, while size, charge, and aromaticity had little impact.
BACKGROUND: Mutations in the CHC (especially at Phe19 and Phe20) have been used to examine the relative impact of hydrophobicity and aromaticity on the degree of aggregation of Aβ(1-42). However, the results have not been conclusive.
METHODS: Partial least squares (PLS) modeling of aggregation rates, using reduced properties of a series of position 19 mutants, was employed to identify the physicochemical properties that had the greatest impact on the extent of aggregation.
RESULTS: The PLS models indicate that hydrophobicity at position 19 of Aβ(1-42) appears to be the primary and dominant factor in controlling Aβ(1-42) aggregation, with aromaticity having little effect.
CONCLUSIONS: This study illustrates the value of using reduced properties of amino acids in conjunction with PLS modeling to investigate mutational effects in peptides and proteins, as the reduced properties can capture in a quantitative manner the different physicochemical properties of the amino acid side chains. In this particular study, hydrophobicity at position 19 was determined to be the dominant property controlling aggregation, while size, charge, and aromaticity had little impact.
摘要：
背景：芳香性与芳香性的重要性中心疏水核的疏水性(CHC，残基17-20）在控制Aβ（1-42）中的原纤维形成方面一直是文献中正在进行的辩论的焦点。
背景：CHC中的突变（尤其是在Phe19和Phe20中）已用于检查疏水性和芳香性对Aβ（1-42）聚集程度的相对影响。然而,结果还没有定论。
方法：聚合率的偏最小二乘(PLS)建模，使用一系列19位突变体的还原特性，用于鉴定对聚集程度影响最大的物理化学性质。
结果：PLS模型表明，Aβ（1-42）19位的疏水性似乎是控制Aβ（1-42）聚集的主要和主导因素，芳香性影响不大。
结论：本研究说明了将氨基酸的降低特性与PLS模型结合使用来研究肽和蛋白质的突变效应的价值。因为降低的性质可以以定量方式捕获氨基酸侧链的不同物理化学性质。在这项特殊的研究中，19位的疏水性被确定为控制聚集的主要性质，虽然大小，charge,芳香性影响不大。
背景：CHC中的突变（尤其是在Phe19和Phe20中）已用于检查疏水性和芳香性对Aβ（1-42）聚集程度的相对影响。然而,结果还没有定论。
方法：聚合率的偏最小二乘(PLS)建模，使用一系列19位突变体的还原特性，用于鉴定对聚集程度影响最大的物理化学性质。
结果：PLS模型表明，Aβ（1-42）19位的疏水性似乎是控制Aβ（1-42）聚集的主要和主导因素，芳香性影响不大。
结论：本研究说明了将氨基酸的降低特性与PLS模型结合使用来研究肽和蛋白质的突变效应的价值。因为降低的性质可以以定量方式捕获氨基酸侧链的不同物理化学性质。在这项特殊的研究中，19位的疏水性被确定为控制聚集的主要性质，虽然大小，charge,芳香性影响不大。
