Unraveling solvent-driven equilibria between α- and 310-helices through an integrated spin Labeling and computational approach
Unraveling solvent-driven equilibria between α- and 310-helices through an integrated spin Labeling and computational approach
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DOI：
10.1021/ja073516s
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发表时间：
2007-09-12
影响因子：
15
通讯作者：
Barone, Vincenzo
中科院分区：
文献类型：
--
作者：
Carlotto, Silvia;Cimino, Paola;Barone, Vincenzo
在这项工作中，我们提出了一个有效的和灵活的计算方法，这是一个正在进行的发展，在我们的小组的结果，允许完整的先验模拟的ESR光谱的复杂系统的解决方案。该方法的有用性和可靠性在非常苛刻的操场上得到了证明，所述操场由不同溶剂的多肽的3（10-）和α-螺旋之间的平衡的调谐所代表。出发点是双自旋标记的七肽Fmoc-（Aib-AibTOAC）（2）-Aib-OMe所采用的3（10-）螺旋的计算结构和X射线衍射结构之间的良好一致性。接下来，密度泛函计算，包括分散体相互作用和散装溶剂的影响，建议另一个能量最小值对应于一个α-螺旋在极性溶剂中，最终，成为最稳定的结构。磁和扩散张量的计算提供了基于随机刘维尔方程（SLE）的方法建立完整光谱的基本成分。在不同温度下的计算和实验光谱之间的显着协议，使我们能够确定在各种溶剂中的螺旋结构。计算策略的通用性及其在有效和用户友好的计算机代码中的实现为生物分子和其他复杂系统领域的系统应用铺平了道路。
In this work we present an effective and flexible computational approach, which is the result of an ongoing development in our groups, allowing the complete a priori simulation of the ESR spectra of complex systems in solution. The usefulness and reliability of the method are demonstrated on the very demanding playground represented by the tuning of the equilibrium between 3(10-) and alpha-helices of polypepticles by different solvents. The starting point is the good agreement between computed and X-ray diffraction structures for the 3(10-)helix adopted by the double spin-labelled heptapeptide Fmoc-(Aib-AibTOAC)(2)-Aib-OMe. Next, density functional computations, including dispersion interactions and bulk solvent effects, suggest another energy minimum corresponding to an alpha-helix in polar solvents, which, eventually, becomes the most stable structure. Computation of magnetic and diffusion tensors provides the basic ingredients for the building of complete spectra by methods rooted in the Stochastic Liouville Equation (SLE). The remarkable agreement between computed and experimental spectra at different temperatures allowed us to identify helical structures in the various solvents. The generality of the computational strategy and its implementation in effective and user-friendly computer codes pave the route toward systematic applications in the field of biomolecules and other complex systems.