Transfer free energy (TFE) of amino acid side-chains from aqueous environment into lipid bilayers is an important energetic factor in determining the thermodynamic stability of a transmembrane protein (TMP). It also provides the basis for understanding TMP folding, membrane insertion, and structure-function relationship. We have derived a General Transfer Free Energy Profile (GeTFEP) from β-barrel transmembrane proteins (TMBs). GeTFEP has a good agreement with previous data measured experimentally or derived computationally. Besides, we show that GeTFEP is applicable to α-helical transmembrane proteins (TMHs) as well by successfully predicting the number and length of transmembrane segments Application of GeTFEP reveals insights into the folding and insertion processes of TMBs. Furthermore, we can predict structurally and/or functionally interesting sites of TMBs using GeTFEP.

GeTFEP: A general transfer free energy profile of transmembrane proteins