Abstract
Free energy of transferring amino acid side–chains from aqueous environment into lipid bilayers, known as transfer free energy (TFE), provides important information on the thermodynamic stability of membrane proteins. In this study, we derived a TFE profile named General Transfer Free Energy Profile (GeTFEP) based on computation of the TFEs of 58 β–barrel membrane proteins (βMPs). The GeTFEP agrees well with experimentally measured and computationally derived TFEs. Analysis based on the GeTFEP shows that residues in different regions of the TM segments of βMPs have different roles during the membrane insertion process. Results further reveal the importance of the sequence pattern of transmembrane strands in stabilizing βMPs in the membrane environment. In addition, we show that GeTFEP can be used to predict the positioning and the orientation of βMPs in the membrane. We also show that GeTFEP can be used to identify structurally or functionally important amino acid residue sites of βMPs. Furthermore, the TM segments of α–helical membrane proteins can be accurately predicted with GeTFEP, suggesting that the GeTFEP captures fundamental thermodynamic properties of amino acid residues inside membrane, and is of general applicability in studying membrane protein.
