Guanine base stacking in G-quadruplex nucleic acids.
Guanine base stacking in G-quadruplex nucleic acids.
复制标题
鸟嘌呤碱基在G-四链体核酸中堆叠。
DOI：
10.1093/nar/gks1110
复制
发表时间：
2013-02-01
影响因子：
14.9
通讯作者：
Phan AT
中科院分区：
文献类型：
--
作者：
Lech CJ;Heddi B;Phan AT
G-四联体构成一类由堆叠的鸟嘌呤四分体（或G-四分体）定义的核酸结构，其中相邻四分体的鸟嘌呤碱基在G-四分体核心内彼此堆叠。单个 G-四链体还可以在其 G-四分体界面处彼此堆叠，从而形成更高阶的结构，如在含有端粒重复的 DNA 和 RNA 中观察到的那样。在这项研究中，我们研究了鸟嘌呤碱基堆积如何影响 G-四链体及其堆积的高阶结构的稳定性。对蛋白质数据库进行了结构调查，以表征实验观察到的 G-四链体核心内以及堆积的 G-四链体结构之间的界面处的鸟嘌呤碱基堆积几何形状。我们将这项调查与使用量子力学计算对堆叠 G-四分体能量景观进行系统计算检查结合起来。堆叠 G-四联体的能量计算表明，在堆叠 G-四联体界面处实验观察到的几何形状之间存在高达 12 kcal/mol 的巨大能量差异。能量景观也使用堆叠能量的 AMBER 分子力学描述进行计算，并且与量子力学计算的景观非常吻合。分子动力学模拟为实验观察到的平行 G 四链体偏好以 5'–5' 方式堆叠提供了结构解释，基于 5'–5' 和 3'–3' 堆叠 G-四链体堆叠界面处不同的可访问四分体堆叠模式。
G-quadruplexes constitute a class of nucleic acid structures defined by stacked guanine tetrads (or G-tetrads) with guanine bases from neighboring tetrads stacking with one another within the G-tetrad core. Individual G-quadruplexes can also stack with one another at their G-tetrad interface leading to higher-order structures as observed in telomeric repeat-containing DNA and RNA. In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally observed geometries at the interface of stacked G-quadruplexes. Energy landscapes are also computed using an AMBER molecular mechanics description of stacking energy and are shown to agree quite well with quantum mechanical calculated landscapes. Molecular dynamics simulations provide a structural explanation for the experimentally observed preference of parallel G-quadruplexes to stack in a 5′–5′ manner based on different accessible tetrad stacking modes at the stacking interfaces of 5′–5′ and 3′–3′ stacked G-quadruplexes.
登录
查看更多内容
影响因子：
14.9
作者：
Cang X;Šponer J;Cheatham TE 3rd
通讯作者：
Cheatham TE 3rd
影响因子：
2.9
作者：
Gu, JD;Leszczynski, J
通讯作者：
Leszczynski, J
影响因子：
14.9
作者：
Cáceres, C;Wright, G;Subirana, JA
通讯作者：
Subirana, JA
影响因子：
14.9
作者：
Collie GW;Haider SM;Neidle S;Parkinson GN
通讯作者：
Parkinson GN
DOI：
10.1039/c0cp00111b
发表时间：
2010-07-28
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Dupradeau FY;Pigache A;Zaffran T;Savineau C;Lelong R;Grivel N;Lelong D;Rosanski W;Cieplak P
通讯作者：
Cieplak P