Force field refinement from NMR scalar couplings

NMR observables contain valuable information about the protein dynamics sampling a high-dimensional potential energy surface. Depending on the observable, the dynamics is sensitive to different time-windows. Scalar coupling constants (h3)J(NC') reflect the pico- to nanosecond motions associated with the intermolecular hydrogen bond network. Including an explicit H-bond in the molecular mechanics with proton transfer (MMPT) potential allows us to reproduce experimentally determined (h3)J(NC') couplings to within 0.02 Hz at best for ubiquitin and protein G. This is based on taking account of the chemically changing environment by grouping the H-bonds into up to seven classes. However, grouping them into two classes already reduces the RMSD between computed and observed (h3)J(NC') couplings by almost 50%. Thus, using ensemble-averaged data with two classes of H-bonds leads to substantially improved scalar couplings from simulations with accurate force fields. (C) 2011 Elsevier B. V. All rights reserved.