Preferential interactions of guanidinum ions with aromatic groups over aliphatic groups.
Preferential interactions of guanidinum ions with aromatic groups over aliphatic groups.
复制标题
DOI：
10.1021/ja903478s
复制
发表时间：
2009-11-25
影响因子：
15
通讯作者：
Brady, John W.
中科院分区：
文献类型：
--
作者：
Mason, Philip E.;Dempsey, Christopher E.;Neilson, George W.;Kline, Steve R.;Brady, John W.
采用小角中子散射（SANS）和分子动力学（MD）模拟研究了异丙醇（IPA）和吡啶水溶液的长程结构（聚集），以及氯化胍（GdmCl）对溶液结构的影响.这些溶质作为蛋白质的非极性脂肪族（IPA）和芳香族（吡啶）侧链的高度可溶性类似物。SANS数据表明，异丙醇和吡啶都形成集群在水中产生的溶质的非极性基团之间的相互作用，吡啶聚集产生更长的范围结构比异丙醇在3摩尔浓度的解决方案。在3摩尔浓度的GdmCl的加入大大减少吡啶聚集，但对异丙醇聚集没有影响。这些解决方案的MD模拟支持的结论是，长程结构涉及疏水性溶质相互作用，和GDM+与平面吡啶基团相互作用，以抑制吡啶-吡啶在溶液中的相互作用。涉及异丙醇的脂肪族基团的疏水相互作用不受GdmCl的影响，这表明平面和弱水合Gdm+阳离子不能与该溶质的高度弯曲或“luorescent”脂肪族基团进行有效的相互作用。这些观察结果支持这样的结论，即Gdm+离子对涉及芳香族氨基酸侧链的蛋白质稳定相互作用的影响对GdmCl的变性剂活性做出了重大贡献，而与“luorescent”脂肪族侧链的相互作用可能不那么重要。
Small angle neutron scattering (SANS) and molecular dynamics (MD) simulations were used to characterize the long range structuring (aggregation) of aqueous solutions of isopropanol (IPA) and pyridine, and the effect on structuring of guanidinium chloride (GdmCl). These solutes serve as highly soluble analogs of the non-polar aliphatic (IPA), and aromatic (pyridine) side chains of proteins. SANS data showed that isopropanol and pyridine both form clusters in water resulting from interaction between non-polar groups of the solutes, with pyridine aggregation producing longer-range structuring than isopropanol in 3 molal solutions. Addition of GdmCl at 3 molal concentration considerably reduced pyridine aggregation, but had no effect on isopropanol aggregation. MD simulations of these solutions support the conclusion that long range structuring involves hydrophobic solute interactions, and that Gdm+ interacts with the planar pyridine group to suppress pyridine-pyridine interactions in solution. Hydrophobic interactions involving the aliphatic groups of isopropanol were unaffected by GdmCl, indicating that the planar and weakly hydrated Gdm+ cation cannot make productive interactions with the highly curved or “lumpy” aliphatic groups of this solute. These observations support the conclusion that the effects of Gdm+ ions on protein-stabilizing interactions involving aromatic amino acid side chains make significant contributions to the denaturant activity of GdmCl, whereas interactions with the “lumpy” aliphatic side chains are likely to be less important.
登录
查看更多内容
影响因子：
2.9
作者：
LEE J C;TIMASHEFF S N
通讯作者：
TIMASHEFF S N
DOI：
10.1073/pnas.0812588106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Lim, Woon Ki;Rosgen, Jorg;Englander, S. Walter
通讯作者：
Englander, S. Walter
影响因子：
2.9
作者：
Dempsey, CE;Piggot, TJ;Mason, PE
通讯作者：
Mason, PE
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML