Accurate structure and dynamics of the metal-site of paramagnetic metalloproteins from NMR parameters using natural bond orbitals.
Accurate structure and dynamics of the metal-site of paramagnetic metalloproteins from NMR parameters using natural bond orbitals.
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DOI：
10.1021/ja209348p
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发表时间：
2012-03-14
影响因子：
15
通讯作者：
Led, Jens J.
中科院分区：
文献类型：
--
作者：
Hansen, D. Flemming;Westler, William M.;Kunze, Micha B. A.;Markley, John L.;Weinhold, Frank;Led, Jens J.
提出了一种金属蛋白质中未成对电子自旋密度的自然键轨道（NBO）分析方法，该方法可以快速、稳健地计算顺磁NMR参数。大约90%的未成对电子自旋密度占据金属配体NBO，允许大部分密度仅由反映化学键合环境的少数NBO建模。我们表明，质子的顺磁弛豫速率可以准确地计算只使用金属配体NBO，这些速率与实验测得的相应速率是很好的协议。这一点尤其适用于点偶极近似失效的配体残基的质子。为了描述重核的顺磁弛豫，还必须考虑局域轨道中的电子自旋密度。15 N的几何距离限制可以从顺磁弛豫增强和费米接触位移时，本地NBO包括在分析中。因此，NBO方法允许我们包括15N核的实验顺磁NMR参数作为结构优化协议中的约束。我们进行了分子动力学模拟和结构测定的氧化rubredoxin使用实验获得的顺磁NMR参数的15 N。所获得的相应结构与rubredoxin的晶体结构一致。因此，NBO的方法允许一个准确的描述的几何结构和动力学的金属蛋白质，当NMR参数是在紧邻的金属网站的核。
A natural bond orbital (NBO) analysis of unpaired electron spin density in metalloproteins is presented, which allows a fast and robust calculation of paramagnetic NMR parameters. Approximately 90% of the unpaired electron spin density occupies metal–ligand NBOs, allowing the majority of the density to be modeled by only a few NBOs that reflect the chemical bonding environment. We show that the paramagnetic relaxation rate of protons can be calculated accurately using only the metal–ligand NBOs and that these rates are in good agreement with corresponding rates measured experimentally. This holds, in particular, for protons of ligand residues where the point-dipole approximation breaks down. To describe the paramagnetic relaxation of heavy nuclei, also the electron spin density in the local orbitals must be taken into account. Geometric distance restraints for 15N can be derived from the paramagnetic relaxation enhancement and the Fermi contact shift when local NBOs are included in the analysis. Thus, the NBO approach allows us to include experimental paramagnetic NMR parameters of 15N nuclei as restraints in a structure optimization protocol. We performed a molecular dynamics simulation and structure determination of oxidized rubredoxin using the experimentally obtained paramagnetic NMR parameters of 15N. The corresponding structures obtained are in good agreement with the crystal structure of rubredoxin. Thus, the NBO approach allows an accurate description of the geometric structure and the dynamics of metalloproteins, when NMR parameters are available of nuclei in the immediate vicinity of the metal-site.
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影响因子：
2.9
作者：
BERTINI, I;GORI, G;VILA, AJ
通讯作者：
VILA, AJ
DOI：
10.1073/pnas.0610313104
发表时间：
2007-06-05
影响因子：
11.1
作者：
Cavalli, Andrea;Salvatella, Xavier;Vendruscolo, Michele
通讯作者：
Vendruscolo, Michele
影响因子：
5.6
作者：
Ganguly, Debabani;Chen, Jianhan
通讯作者：
Chen, Jianhan
影响因子：
2.7
作者：
Banci, L;Bertini, I;Parigi, G
通讯作者：
Parigi, G
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD