  This review describes recent advances by the authors and others on the topic
of incorporating experimental data into molecular simulations through maximum
entropy methods. Methods which incorporate experimental data improve accuracy
in molecular simulation by minimally modifying the thermodynamic ensemble. This
is especially important where force fields are approximate, such as when
employing coarse-grain models, or where high accuracy is required, such as when
attempting to mimic a multiscale self-assembly process. The authors review here
the experiment directed simulation (EDS) and experiment directed metadynamics
(EDM) methods that allow matching averages and distributions in simulations,
respectively. Important system-specific considerations are discussed such as
using enhanced sampling simultaneously, the role of pressure, treating
uncertainty, and implementations of these methods. Recent examples of EDS and
EDM are reviewed including applications to ab initio molecular dynamics of
water, incorporating environmental fluctuations inside of a macromolecular
protein complex, improving RNA force fields, and the combination of enhanced
sampling with minimal biasing to model peptides.
