Fitting Force Field Parameters to NMR Relaxation Data

• DOI: 10.1021/acs.jctc.3c00174
• Publication Date: 2023-06-05T16:07:03Z
• Authors: Felix Kümmerer; Simone Orioli; Kresten Lindorff-...
• Keywords: Magnetic Resonance Spectroscopy; Ubiquitin; Proteins; Molecular Dynamics Simulation; Nuclear Magnetic Resonance, Biomolecular; 01 natural sciences; 0104 chemical sciences

AbstractWe present an approach to optimise force field parameters using time-dependent data from NMR relaxation experiments. To do so, we scan parameters in the dihedral angle potential energy terms describing the rotation of the methyl groups in proteins, and compare NMR relaxation rates calculated from molecular dynamics simulations with the modified force fields to deuterium relaxation measurements of T4 lysozyme. We find that a small modification of Cγmethyl groups improves the agreement with experiments both for the protein used to optimize the force field, and when validating using simulations of CI2 and ubiquitin. We also show that these improvements enable a more effectivea posteriorireweighting of the MD trajectories. The resulting force field thus enables more direct comparison between simulations and side-chain NMR relaxation data, and makes it possible to construct ensembles that better represent the dynamics of proteins in solution.