The energy landscape for protein folding and possible connections to function

In this article we review and discuss the state-of-the-art methods using minimalist models in the context of energy landscape theory to study protein folding. As good agreement between computational/theoretical studies and experimental observations in vitro continues to emerge, many research groups are asking how this structural and dynamical information can be used to understand proteins in vivo. This is a non-trivial question drawing from very limited in vivo studies. From the perspective of theory, it is a new horizon for theoreticians to test or revise their theories by making connections to experiments on this matter. We present a short discussion of several recent efforts that include factors reflecting the cellular environment in computer simulations—and that may provide some insight into the behavior of protein dynamics inside the living cell as well as inspire the development of new experimental approaches for a better understanding of the molecular mechanisms for function.