Pharmacophore Mapping via Cross-Relaxation during Adiabatic Fast Passage
Pharmacophore Mapping via Cross-Relaxation during Adiabatic Fast Passage
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DOI：
10.1021/ja910098s
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发表时间：
2010-02-10
影响因子：
15
通讯作者：
Konrat, Robert
中科院分区：
文献类型：
--
作者：
Auer, Renate;Kloiber, Karin;Konrat, Robert
提出了一种新的核磁共振方法来研究蛋白质配体相互作用。在这种方法中，使用绝热快速通过脉冲，即具有线性扫频的长弱脉冲来探测H-1-H-1 NOEs。在绝热快速通道期间，有效旋转框架NOE是横向和纵向交叉松弛贡献的加权平均值，可以通过脉冲功率和扫频速率进行调节。结果表明，自旋扩散过程的发生导致自旋锁框架中有效弛豫速率和有效倾斜角度的理论关系出现较大偏差，可用于探测蛋白质-配体结合。该方法灵敏度高，易于实现。该技术的可行性通过两种蛋白质复合物进行了验证，即与鹌鹑脂质脂质Q83和NAD（+）结合的香草酸和与乙醇脱氢酶（ADH）结合的AMP。
A novel NMR method is demonstrated for the investigation of protein ligand interactions. In this approach an adiabatic fast passage pulse, i.e. a long, weak pulse with a linear frequency sweep, is used to probe H-1-H-1 NOEs. During the adiabatic fast passage the effective rotating-frame NOE is a weighted average of transverse and longitudinal cross-relaxation contributions that can be tuned by pulse power and frequency sweep rate. It is demonstrated that the occurrence of spin diffusion processes leads to sizable deviations from the theoretical relationship between effective relaxation rate and effective tilt angle in the spin lock frame and can be used to probe protein-ligand binding. This methodology comprises high sensitivity and ease of implementation. The feasibility of this technique is demonstrated with two protein complexes, vanillic acid bound to the quail lipocalin Q83 and NAD(+) and AMP binding to alcohol dehydrogenase (ADH).