Multibody Terms in Protein Coarse-Grained Models: A Top-Down Perspective

Coarse-grained models allow computational investigationof biomolecularprocesses occurring on long time and length scales, intractable withatomistic simulation. Traditionally, many coarse-grained models relymostly on pairwise interaction potentials. However, the decimationof degrees of freedom should, in principle, lead to a complex many-bodyeffective interaction potential. In this work, we use experimentaldata on mutant stability to parametrize coarse-grained models fortwo proteins with and without many-body terms. We demonstrate thatmany-body terms are necessary to reproduce quantitatively the effectsof point mutations on protein stability, particularly to implicitlytake into account the effect of the solvent.

Automated summary

Coarse-grained models are useful for studying biomolecular processes on long time and length scales. In this study, experimental data on mutant stability is used to develop coarse-grained models for two proteins, with and without many-body terms. It is shown that many-body terms are necessary to accurately simulate the effect of point mutations on protein stability, particularly considering the solvent effect.