Fragment-based quantum chemical calculations using our adjustable density matrix assembler (ADMA) approach are able to calculate NMR chemical shifts even for proteins, DNA/RNA molecules and their complexes. The agreement between the calculated and experimental chemical shifts in these calculations can be highly increased if they are not only based on a single (experimental) structure but if conformational sampling and explicit solvent molecules are included. Thermodynamic ensembles taken from classical molecular dynamics (MD) simulations are suited for 13C and 1H chemical shift calculations if polar protons are neglected. Input structures from a Car�Parrinello MD result in additional landmark improvements over calculations based on classical MD especially for amide protons, which are predicted too high-field shifted based on the latter ensembles. The better results are caused by the solute�solvents interactions forming shorter hydrogen bonds as well as by the internal degrees of freedom of the solute. With the obtained accuracy and the possibility of identifying the structural reasons for discrepancies between the experimental and calculated data, NMR chemical-shift calculations can, on the one hand, now be used to validate NMR structures and are, on the other hand, a perfect criterion for e.g. the development of new, improved force fields.

Importance of conformational sampling and solvent effects on the quantum-chemical calculation of NMR chemical shifts in biomolecular systems

248th National Meeting (2014)

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