Abstract
Transfer free energy (TFE) of amino acid side-chains from aqueous environment into lipid bilayers is an important contributing 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 is in good agreement with previous experimentally measured and computationally derived scales. 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 significant insights into the folding and insertion processes of TMBs. Furthermore, we can predict structurally and/or functionally interesting sites of TMBs using GeTFEP.