CSGT-DFT calculation of 13C and 15N NMR shielding of the backbone amide group, 13Cα, and 13Cβ in ω-Conotoxin GVIA

Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. 3. Conformational Sampling and Explicit Solvents Model

“…We and others have realized in previous studies − that QM calculations of proteins and peptides yield unsatisfactory results for CO and H N and N H most likely due to influences of the solvent, hydrogen bonding, and/or conformational averaging that are not properly reflected in the QM approach. To gain insight in this regard, we performed a detailed investigation with NMA.…”

“…Even if solvent effects have been included already in calculations on proteins using implicit solvent models, ,, the consideration of explicit solvent molecules has proven to be needed for the accurate chemical shift calculations of small molecules, ,− especially in the case of hydrogen bonding between solvent and solute. Additionally, it was shown that the effects of small conformational changes including zero-point vibration are relevant for small molecules, ,,,− and we expect that this is even more the case in large biomolecular systems and especially within flexible loops of proteins. To account for these effects in our calculations, we performed classical molecular dynamics (MD) simulations and extracted solute conformations with their correspondent solvent shells from these.…”

“…To support such investigations, accurate predictions of NMR chemical shifts are of great benefit since they can be used for structure evaluation and validation and linking NMR chemical shift perturbations to conformational changes. Due to advanced developments in the theoretical treatment but also to the formidable increase in computer power available, quantum mechanical NMR chemical shift calculations can now reach the accuracy needed for these applications, as demonstrated in a number of recent publications, − including the first two parts of this series of papers from our group. , Since the small review of methods in the introduction of the second part, important new contributions have been made, which will be shortly highlighted here. Flaig et al studied the influence of the size of the quantum mechanical region in a QM/MM approach on the calculated chemical shifts.…”

Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. 2. Level of Theory, Basis Set, and Solvents Model Dependence

“…This work was then continued and extended by de Dios and co-workers. 10,26 The group of Scheraga [13][14][15][16]34 developed a method for protein NMR structure determination, refinement, and validation based on quantum chemical 13 C α chemical shifts calculated for a large number of different conformations of the central residues in tripeptides.…”

Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions

“…Besides their much higher efficiency as compared to quantum-chemical calculations, this is justified by the claim that the quantum mechanical methods available for such large systems are not accurate enough . Nevertheless, recent studies − have clearly demonstrated that the main errors are not associated with the levels of theory and the basis sets used but arise from the neglect of conformational averaging and first-solvent-shell effects. In our previous paper, we were able to show that NMR chemical shifts of nonpolar protons and carbon atoms in proteins can be calculated with unprecedented accuracy in a purely structure-based approach if multiple structures are taken from molecular dynamics simulations and explicit solvent molecules are considered.…”