Generating properly weighted ensemble of conformations of proteins from sparse or indirect distance constraints.
Generating properly weighted ensemble of conformations of proteins from sparse or indirect distance constraints.
复制标题
DOI：
10.1063/1.2968605
复制
发表时间：
2008-09-07
期刊：
影响因子：
--
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Lin M;Lu HM;Chen R;Liang J
从有限的实验数据中推断蛋白质等生物大分子的三维结构信息是一项重要而具有挑战性的任务。基于核磁共振、二硫键连接和电子顺磁共振标记研究的核Overhauser效应(NOE)测量都可以提供有用的蛋白质构象特征的部分距离约束。在这项研究中，我们描述了一种重建生物分子构象的一般方法，该方法符合给定的距离限制。这种约束可以是残基对之间距离的上界和下界、基于特定接触距离截止值的接触图或诸如实验ϕ值测量的间接距离约束的形式。我们的方法是基于序贯蒙特卡罗方法的框架，这是一种基于链增长的方法。我们开发了一种新的生长势函数来指导满足给定距离限制的构象的生成。该势函数不仅包含了当前残基在生长过程中的距离信息，而且通过引入残基对之间的全局距离上界和参考点的放置，还包含了未来残基的距离信息。为了从间接距离约束中获得实验ϕ值形式的蛋白质构象，我们首先生成满足ϕ值约束的适当加权的接触图，然后从这些接触图生成构象。我们证明了我们的方法可以忠实地生成满足给定约束的构象，当所有剩余对的距离约束给定时，这些构象接近于自然结构。
Inferring three-dimensional structural information of biomacromolecules such as proteins from limited experimental data is an important and challenging task. Nuclear Overhauser effect (NOE) measurements based on nucleic magnetic resonance, disulfide linking, and electron paramagnetic resonance labelling studies can all provide useful partial distance constraints characteristic of the conformations of proteins. In this study, we describe a general approach for reconstructing conformations of biomolecules that are consistent with given distance constraints. Such constraints can be in the form of upper bounds and lower bounds of distances between residue pairs, contact maps based on specific contact distance cut-off values, or indirect distance constraints such as experimental ϕ-value measurement. Our approach is based on the framework of sequential Monte Carlo method, a chain growth-based method. We have developed a novel growth potential function to guide the generation of conformations that satisfy given distance constraints. This potential function incorporates not only distance information of current residue during growth, but also distance information of future residue by introducing global distance upper bounds between residue pairs and the placement of reference points. To obtain protein conformations from indirect distance constraints in the form of experimental ϕ-values, we first generate properly weighted contact maps satisfying ϕ-value constraints, we then generate conformations from these contact maps. We show our approach can faithfully generate conformations that satisfy the given constraints, which approach the native structures when distance constraints for all residue pairs are given.
登录
查看更多内容
影响因子：
2.9
作者：
JACKSON, SE;MORACCI, M;FERSHT, AR
通讯作者：
FERSHT, AR
影响因子：
2.9
作者：
Falcon, CM;Matthews, KS
通讯作者：
Matthews, KS
DOI：
10.1073/pnas.94.26.14267
发表时间：
1997-12-23
影响因子：
11.1
作者：
Cai, KW;Langen, R;Khorana, HG
通讯作者：
Khorana, HG
DOI：
10.1073/pnas.91.22.10426
发表时间：
1994-10-25
影响因子：
11.1
作者：
FERSHT, AR;ITZHAKI, LS;OTZEN, DE
通讯作者：
OTZEN, DE
影响因子：
2.9
作者：
Altenbach, C;Oh, KJ;Hubbell, WL
通讯作者：
Hubbell, WL