Fundamental to the central goals of structural biology is knowledge of the energetics of molecular interactions. Because membrane proteins reside in a free energy minimum dictated by their sequences, their lipid environment, and water, one must understand the energetics of membrane protein folding to generate physical descriptions of cellular processes. Several technical obstacles have recently been overcome to enable folding measurements for membrane proteins in lipid and detergent micelle environments, and several new folding free energies have been published within the past ten years. This review discusses the challenges, successes, and novel insights into the physical basis underlying membrane protein folds.


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