Force field (fiction)

Optics

Physics

Small-angle X-ray scattering

Computational chemistry

Artificial intelligence

Chemical physics

Neuroscience

Chemistry

Scattering

Materials science

Relaxation (psychology)

Intrinsically disordered proteins

Computer science

Nuclear magnetic resonance

Molecular dynamics

Crystallography

Biology

Journal of Chemical Theory and Computation

Coarse-grained molecular dynamics simulations are a useful tool to determine conformational ensembles of proteins. Here, we show that the coarse-grained force field Martini 3 underestimates the global dimensions of intrinsically disordered proteins (IDPs) and multidomain proteins when compared with small-angle X-ray scattering (SAXS) data and that increasing the strength of protein-water interactions favors more expanded conformations. We find that increasing the strength of interactions between protein and water by ca. 10% results in improved agreement with the SAXS data for IDPs and multidomain proteins. We also show that this correction results in a more accurate description of self-association of IDPs and folded proteins and better agreement with paramagnetic relaxation enhancement data for most IDPs. While simulations with this revised force field still show deviations to experiments for some systems, our results suggest that it is overall a substantial improvement for coarse-grained simulations of soluble proteins.

Improving Martini 3 for Disordered and Multidomain Proteins