  The protein chemical shifts holds a large amount of information about the
3-dimensional structure of the protein. A number of chemical shift predictors
based on the relationship between structures resolved with X-ray
crystallography and the corresponding experimental chemical shifts have been
developed. These empirical predictors are very accurate on X-ray structures but
tends to be insensitive to small structural changes. To overcome this
limitation it has been suggested to make chemical shift predictors based on
quantum mechanical(QM) calculations. In this thesis the development of the QM
derived chemical shift predictor Procs14 is presented. Procs14 is based on 2.35
million density functional theory(DFT) calculations on tripeptides and contains
corrections for hydrogen bonding, ring current and the effect of the previous
and following residue. Procs14 is capable at performing predictions for the
13CA, 13CB, 13CO, 15NH, 1HN and 1HA backbone atoms. In order to benchmark
Procs14, a number of QM NMR calculations are performed on full protein
structures. Of the tested empirical and QM derived predictors, Procs14
reproduced the QM chemical shifts with the highest accuracy. A comparison with
the QM derived predictor CheShift-2 on X-ray structures and NMR ensembles with
experimental chemical shift data, showed that Procs14 predicted the chemical
shifts with the best accuracy. The predictions on the NMR ensembles exhibited
the best performance. This suggests that future work might benefit from using
ensemble sampling when performing simulations of protein folding with chemical
shifts. Procs14 is implemented in the markov chain monte carlo protein folding
framework PHAISTOS. The computational efficient implementation of Procs14
allows for rapid predictions and therefore potential use in refinement and
folding of protein structures.
