Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
J Chem Theory Comput. 2008 Nov 11;4(11):1949-58. doi: 10.1021/ct800241d.
The ability to measure scalar coupling constants across hydrogen bonds ((3h)JNC') from high-resolution NMR experiments allows the characterization of detailed structural properties of biomolecules. To analyze those, a parametrized model based on the linear combination of atomic orbitals relates H-bond geometries with the measured (3h)JNC' coupling magnitude. In the present study the dependence of calculated (3h)JNC' coupling constants on force field parameters is assessed. It is shown that increased polarity of the hydrogen bond improves the calculated (3h)JNC' coupling constants and shifts the conformational ensemble sampled from the molecular dynamics (MD) simulations toward the experimentally measured one. Increased charges lead to more narrow distance and angle distributions and improve the agreement between calculated and measured (3h)JNC' couplings. However, different secondary structures are better represented by different magnitudes of electrostatic interactions-different atomic partial charges in the present work-as indicated by root-mean square deviations (rsmds) between observed and calculated coupling constants (3h)JNC'. The parametrization of the empirical formula is found to be meaningful and robust, but the parameter values are not universal across different proteins and different secondary structural elements (α-helices, β-sheets and loops). Using standard and slightly increased CHARMM charges, predictions for the as-yet unknown scalar coupling constants for the V54A and I6A mutants of protein G are made.
从高分辨率 NMR 实验中测量氢键（(3h)JNC'）的标量耦合常数的能力允许对生物分子的详细结构特性进行表征。为了分析这些特性，一种基于原子轨道线性组合的参数化模型将氢键几何形状与测量的(3h)JNC'耦合强度联系起来。在本研究中，评估了计算得到的(3h)JNC'耦合常数对力场参数的依赖性。结果表明，氢键的极性增加会提高计算得到的(3h)JNC'耦合常数，并使从分子动力学（MD）模拟中采样的构象集合向实验测量的构象集合移动。增加电荷会导致距离和角度分布更窄，并提高计算和测量的(3h)JNC'耦合之间的一致性。然而，不同的二级结构由不同大小的静电相互作用（本工作中的不同原子部分电荷）更好地表示，这由观察到的和计算得到的耦合常数（(3h)JNC'）之间的均方根偏差（rsmd）表示。发现经验公式的参数化是有意义和稳健的，但参数值不是普遍适用于不同的蛋白质和不同的二级结构元件（α-螺旋、β-折叠和环）。使用标准和略微增加的 CHARMM 电荷，对蛋白质 G 的 V54A 和 I6A 突变体的未知标量耦合常数进行了预测。
