Conformational Space of Flexible Biological Macromolecules from Average Data
Conformational Space of Flexible Biological Macromolecules from Average Data
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DOI：
10.1021/ja1063923
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发表时间：
2010-09-29
影响因子：
15
通讯作者：
Svergun, Dmitri I.
中科院分区：
文献类型：
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作者：
Bertini, Ivano;Giachetti, Andrea;Svergun, Dmitri I.
引入了最大发生（MO）的概念，即柔性蛋白质在任何给定构象中所能花费的最大时间百分比，并开发了一种严格的方法来广泛采样构象空间并从实验数据构建MO图。该方法在柔性双结构域蛋白钙调素（CaM）的案例研究中进行了测试，使用SAXS和NMR数据（即，由顺磁性镧系离子存在引起的假接触位移和自取向残余偶极偶联），揭示了捕获在CaM晶体形式中的“封闭”和“完全扩展”构象的MOs分别仅为5%和15%。紧凑型构象的MO一般较小，而一些扩展构象的MO高达35%，强烈表明这些构象在溶液中最丰富。该方法是普遍适用的，因为它只需要标准的SAXS数据和蛋白质的镧系衍生物的特定NMR数据（使用天然金属位点或镧系标记）。计算机程序可以通过作者的Web门户通过网格计算基础设施公开获得。
The concept of maximum occurrence (MO), i.e., the maximum percent of time that flexible proteins can spend in any given conformation, is introduced, and a rigorous method is developed to extensively sample the conformational space and to construct MO maps from experimental data. The method is tested in a case study, the flexible two-domain protein calmodulin (CaM), using SAXS and NMR data (i.e., pseudocontact shifts and self-orientation residual dipolar couplings arising from the presence of paramagnetic lanthanide ions), revealing that the "closed" and "fully extended" conformations trapped in the crystalline forms of CaM have MOs of only 5 and 15%, respectively. Compact conformations in general have small MOs, whereas some extended conformations have MO as high as 35%, strongly suggesting these conformations to be most abundant in solution. The method is universally applicable as it requires only standard SAXS data and specific NMR data on lanthanide derivatives of the protein (using native metal sites or lanthanide tagging). The computer program is publicly available using the grid computing infrastructure through the authors' Web portal.