Toward the quantum chemical calculation of nuclear magnetic resonance chemical shifts of proteins

Abstract

Despite the many protein structures solved successfully by nuclear magnetic resonance (NMR) spectroscopy, quality control of NMR structures is still by far not as well established and standardized as in crystallography. Therefore, there is still the need for new, independent, and unbiased evaluation tools to identify problematic parts and in the best case also to give guidelines that how to fix them. We present here, quantum chemical calculations of NMR chemical shifts for many proteins based on our fragment-based quantum chemical method: the adjustable density matrix assembler (ADMA). These results show that (13)C chemical shifts of reasonable accuracy can be obtained that can already provide a powerful measure for the structure validation. (1)H and even more (15)N chemical shifts deviate more strongly from experiment due to the insufficient treatment of solvent effects and conformational averaging.

Quantum Chemical Calculations of Amide-15N Chemical Shift Anisotropy Tensors for a Membrane-Bound Cytochrome-b5

“…The omission of these effects in the calculation could contribute to the observed discrepancies between calculated and experimental chemical shift values obtained from solution NMR measurements. 56, 68, 69, 74, 100–102 In a previous study a difference of ~5 ppm in experimentally measured isotropic chemical shift values was reported between oxidized and reduced state of cytb 5 . 103 Therefore, the interaction of amide nitrogen with the paramagnetic center of the heme unit could also contribute to the discrepancy.…”

“…The range of calculated isotropic chemical shift values is slightly larger (102.7–134.3 ppm) than the range of experimentally determined values (105.3–130.8 ppm), 35 which is still smaller than the range reported for Tfb1/p53 complex in a recent work. 56 Interestingly, in another report 57 it was shown that the use of 6-311g(d) basis set coupled with B3LYP functional produced larger deviations in comparison to experimental results. However, in the present study, the use of larger basis set 6-311+g(2d,p) on 15 N is shown to reduce the variation when compared to the experimental data.…”

DFT application in conformational determination of cellobiose

“…The chemical shifts are extremely sensitive to structural changes. 36 The accurately predicted 13 C chemical shifts 37-39 provide a powerful measure for the protein structure validation. It is likely that a similar correlation between chemical shifts and carbohydrate structures exists as well though such a study has not been carried out systematically.…”

Converging nuclear magnetic shielding calculations with respect to basis and system size in protein systems

“…Rather, one often performs calculations on a protein sub-cluster surrounding the substrate or region of interest using either a purely quantum mechanical (QM) or a hybrid quantum/ classical molecular mechanics (QM/MM) cluster model. Sometimes multiple such QM/MM calculations are performed using a fragment approach (Zhu et al (2012); Frank et al (2011); Tan and Bettens (2013); Gao et al (2014)). …”