Rapid Computation of Protein NMR Properties - An Optimal Way to Chemical Shift Driven Protein Structure Refinement

Ab initio methods for chemical shift calculation are much too demanding for biopolymers and protein structure refinement. No oh initio chemical shift gradients have been developed up to now. Bond polarization theory (BPT) is a rapid and reliable semi-empirical method for computation of NMR parameters. We adapted BPT to the calculation of protein NMR chemical shifts. BPT routines are included into the COSMOS-NMR hybrid QM/MM force field enabling chemical shift driven geometry optimization. In this paper we describe the development of the protocol for chemical shift driven protein structure refinement and prove its robustness by applying it to seven randomly chosen structures from the RCSB protein data bank.