While these methods attempt to expand the scope of a given simulation method, it is also possible to optimize existing coarse grain approaches with a relative method based on entropy . Many of these advanced sampling methods discussed in this section can also be used in combination to address specific biological modelling problems. Each has in common a reduction in the number of degrees of freedom that makes it possible to simulate large nuclear systems in great detail. In this sense, coarse grain molecular simulations are another improved sampling method, in this case ideal for extending the size and duration of protein simulations. As shown by competing methods of designing and coordinating coarse-grained force fields, there is no single coarse-grained method that can produce the same description as an atomic method. The choice between structural, thermodynamic, and force equalization strategies depends heavily on the system involved, computational resources, experimental objective data, and, most importantly, the question the model needs to answer. Although many of these methods are capable of reproducing a combination of structural and thermodynamic data, there is no guarantee that a naïve coarse grain simulation will yield accurate results. Careful coordination of theory, simulation and experimentation ensures that a particular model is physically accurate. More importantly, the contact between these methods offers a perspective on the physics of biological processes. In particular, we see that double lipid layers transmit a variety of cellular processes, from the action of mechanically sensitive ion channels to the transformation of morphological membranes to the activation of complex networks of cellular signals by membrane-associated proteins. Future studies of protein membrane systems using coarse grain methods will depend on synthesizing our understanding of soft matter systems with biology and biochemistry. This area of research has the potential to improve human health by dissolving high-resolution cell biology processes and further guiding the development of new treatment strategies. .