Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations of Proteins
Using NMR Chemical Shifts as Structural Restraints in Molecular Dynamics Simulations of Proteins
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DOI：
10.1016/j.str.2010.04.016
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发表时间：
2010-08-11
期刊：
影响因子：
5.7
通讯作者：
Vendruscolo, Michele
中科院分区：
文献类型：
--
作者：
Robustelli, Paul;Kohlhoff, Kai;Vendruscolo, Michele
我们介绍了一个程序，以确定蛋白质的结构，将NMR化学位移作为结构的限制，在分子动力学模拟。在这种方法中，化学位移被表示为原子坐标的可微函数，并用于计算力以产生导致实验和计算的化学位移之间的差异减小的轨迹。我们表明，这种策略使一组蛋白质的折叠与代表性的拓扑结构从部分变性的初始构象，而不使用额外的实验信息。这种方法还可以直接将化学位移与其他标准NMR限制结合起来，包括NOE，J-耦合和残余偶极耦合测量。我们说明了这方面通过计算的结构的瞬态填充激发态构象从化学位移和残余偶极耦合数据测量的弛豫色散NMR实验。
We introduce a procedure to determine the structures of proteins by incorporating NMR chemical shifts as structural restraints in molecular dynamics simulations. In this approach, the chemical shifts are expressed as differentiable functions of the atomic coordinates and used to compute forces to generate trajectories that lead to the reduction of the differences between experimental and calculated chemical shifts. We show that this strategy enables the folding of a set of proteins with representative topologies starting from partially denatured initial conformations without the use of additional experimental information. This method also enables the straightforward combination of chemical shifts with other standard NMR restraints, including those derived from NOE, J-coupling, and residual dipolar coupling measurements. We illustrate this aspect by calculating the structure of a transiently populated excited state conformation from chemical shift and residual dipolar coupling data measured by relaxation dispersion NMR experiments.