Contrastive Learning of Coarse-Grained Force Fields

Coarse-grained models have proven helpful for simulating complex systems over long time scales to provide molecular insights into various processes. Methodologies for systematic parametrization of the underlying energy function or force field that describes the interactions among different components of the system are of great interest for ensuring simulation accuracy. We present a new method, potential contrasting, to enable efficient learning of force fields that can accurately reproduce the conformational distribution produced with all-atom simulations. Potential contrasting generalizes the noise contrastive estimation method with umbrella sampling to better learn the complex energy landscape of molecular systems. When applied to the Trp-cage protein, we found that the technique produces force fields that thoroughly capture the thermodynamics of the folding process despite the use of only alpha-carbons in the coarse-grained model. We further showed that potential contrasting could be applied over large data sets that combine the conformational ensembles of many proteins to improve force field transferability. We anticipate potential contrasting as a powerful tool for building general-purpose coarse-grained force fields.

Automated summary

Coarse-grained models are useful for simulating complex systems and providing molecular insights. This study introduces a new method, potential contrasting, for efficiently learning force fields that accurately reproduce the conformational distribution produced by all-atom simulations. The technique has been applied to the Trp-cage protein and shows promise in capturing the thermodynamics of the folding process and improving force field transferability.