Despite extended experimental and computational studies, the mechanism regulating membrane protein folding and stability in cell membranes is not fully understood. In this review, I will provide a personal and partial account of the scientific efforts undertaken by Dr. Stephen White to shed light on this topic. After briefly describing the role of water and the hydrophobic effect on cellular processes, I will discuss the physical chemistry of water confined inside the SecY translocon pore. I conclude with a review of recent literature that attempts to answer fundamental questions on the pathway and energetics of translocon-guided membrane protein insertion.
Keywords: Confined water; Membrane protein folding; Protein-conducting channel.