Systematic design of biomolecular force fields

Force fields for the study of biomolecules have been developed in a predominantly organic manner by regular updates over half a century. Together with better algorithms and advances in computer technology, force fields have improved to yield more robust predictions. However, there are also indications to suggest that intramolecular energy functions have not become better and that there still is room for improvement. In this review, systematic efforts toward development of novel force fields from scratch are described. This includes an estimate of the complexity of the problem and the prerequisites in the form of data and algorithms. It is suggested that in order to make progress, an effort is needed to standardize reference data and force field validation benchmarks.