PPM: a side-chain and backbone chemical shift predictor for the assessment of protein conformational ensembles.

The combination of the wide availability of protein backbone and side-chain NMR chemical shifts with advances in understanding of their relationship to protein structure makes these parameters useful for the assessment of structural-dynamic protein models. A new chemical shift predictor (PPM) is introduced, which is solely based on physical-chemical contributions to the chemical shifts for both the protein backbone and methyl-bearing amino-acid side chains. To explicitly account for the effects of protein dynamics on chemical shifts, PPM was directly refined against 100 ns long molecular dynamics (MD) simulations of 35 proteins with known experimental NMR chemical shifts. It is found that the prediction of methyl-proton chemical shifts by PPM from MD ensembles is improved over other methods, while backbone Cα, Cβ, C', N, and H(N) chemical shifts are predicted at an accuracy comparable to the latest generation of chemical shift prediction programs. PPM is particularly suitable for the rapid evaluation of large protein conformational ensembles on their consistency with experimental NMR data and the possible improvement of protein force fields from chemical shifts.