Integration of experimental data and use of automated fitting methods in developing protein force fields

Molecular dynamics simulations, used to study chemical and biophysical processes, rely on the accuracy of the employed force fields. Here, the authors review successes and key areas of difficulty in the development of additive and polarizable force fields, and discuss experimental data availability, how empirical refinement impacts parametrization, and highlight possible routes to further improve the accuracy of force fields. The development of accurate protein force fields has been the cornerstone of molecular simulations for the past 50 years. During this period, many lessons have been learned regarding the use of experimental target data and parameter fitting procedures. Here, we review recent advances in protein force field development. We discuss the recent emergence of polarizable force fields and the role of electronic polarization and areas in which additive force fields fall short. The use of automated fitting methods and the inclusion of additional experimental solution data during parametrization is discussed as a means to highlight possible routes to improve the accuracy of force fields even further.

Automated summary

This paper reviews the successes and difficulties in the development of additive and polarizable force fields, discusses the availability of experimental data, and highlights possible routes to further improve the accuracy of force fields.