A Nexus between Theory and Experiment: Non-Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋠Guest Binding Interactions.

A training set of eleven X-ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane-/diamantane ammonium/aminium guests were studied with DFT-D3 quantum mechanical computational methods to afford ΔGcalcd binding energies. A novel feature of this work is that the fidelity of the BLYP-D3/def2-TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n]⋅guest complex binding energy subcomponents [for example, ΔEdispersion , ΔEelectrostatic , ΔGsolvation , binding entropy (-TΔS), and induced fit Edeformation(host) , Edeformation(guest) ] were calculated. Only a few weeks of computation time per complex were required by using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n=5, 6, 7, 8) isolated host molecules were also explored by means of the DFT-D3 method. A high ρ2 =0.84 correlation coefficient between ΔGexptl and ΔGcalcd was achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔGcalcd predictions of new complexes. The nature of binding, including the role of high energy water molecules, was also studied. The utility of introduction of tethered [-(CH2 )n NH3 ]+ amino loops attached to N,N-dimethyl-adamantane-1-amine and N,N,N',N'-tetramethyl diamantane-4,9-diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra-high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.

Solution NMR and molecular dynamics reveal a persistent alpha helix within the dynamic region of PsbQ from photosystem II of higher plants.

The extrinsic proteins of photosystem II of higher plants and green algae PsbO, PsbP, PsbQ, and PsbR are essential for stable oxygen production in the oxygen evolving center. In the available X-ray crystallographic structure of higher plant PsbQ residues S14-Y33 are missing. Building on the backbone NMR assignment of PsbQ, which includes this "missing link", we report the extended resonance assignment including side chain atoms. Based on nuclear Overhauser effect spectra a high resolution solution structure of PsbQ with a backbone RMSD of 0.81 Å was obtained from torsion angle dynamics. Within the N-terminal residues 1-45 the solution structure deviates significantly from the X-ray crystallographic one, while the four-helix bundle core found previously is confirmed. A short α-helix is observed in the solution structure at the location where a ß-strand had been proposed in the earlier crystallographic study. NMR relaxation data and unrestrained molecular dynamics simulations corroborate that the N-terminal region behaves as a flexible tail with a persistent short local helical secondary structure, while no indications of forming a ß-strand are found.

Spin-Noise-Detected Two-Dimensional Fourier-Transform NMR Spectroscopy.

We introduce two-dimensional NMR spectroscopy detected by recording and processing the noise originating from nuclei that have not been subjected to any radio frequency excitation. The method relies on cross-correlation of two noise blocks that bracket the evolution and mixing periods. While the sensitivity of the experiment is low in conventional NMR setups, spin-noise-detected NMR spectroscopy has great potential for use with extremely small numbers of spins, thereby opening a way to nanoscale multidimensional NMR spectroscopy.

Backbone assignment and secondary structure of the PsbQ protein from photosystem II.

PsbQ is one of the extrinsic proteins situated on the lumenal surface of photosystem II (PSII) in the higher plants and green algae. Its three-dimensional structure was determined by X-ray crystallography with exception of the residues 14-33. To obtain further details about its structure and potentially its dynamics, we approached the problem by NMR. In this paper we report (1)H, (15)N, and (13)C NMR assignments for the PsbQ protein. The very challenging oligo-proline stretches could be assigned using (13)C-detected NMR experiments that enabled the assignments of twelve out of the thirteen proline residues of PsbQ. The identification of PsbQ secondary structure elements on the basis of our NMR data was accomplished with the programs TALOS+, web server CS23D and CS-Rosetta. To obtain additional secondary structure information, three-bond H(N)-H(α) J-coupling constants and deviation of experimental (13)C(α) and (13)C(ß) chemical shifts from random coil values were determined. The resulting "consensus" secondary structure of PsbQ compares very well with the resolved regions of the published X-ray crystallographic structure and gives a first estimate of the structure of the "missing link" (i.e. residues 14-33), which will serve as the basis for the further investigation of the structure, dynamics and interactions.