Understanding the structural and mechanical properties of transmembrane proteins

Transmembrane proteins (TM) are embedded in cell membranes and play a crucial role in transport, cellular interactions, and signaling. TM proteins account for nearly a third of all natural proteins and serve as targets for a wide array of drug therapies. However, due to a lack of available high-resolution data, many features of the structure of TM proteins are not well known. We analyzed the composition, side chain conformations, and packing fraction of buried residues in TM proteins using available protein crystal structures. We find that buried residues in TM and soluble proteins have similar packing fraction distributions. In addition, we show that the hard-sphere plus stereochemical constraint model is able to recapitulate the side chain dihedral angle conformations of buried residues observed in crystal structures. This result emphasizes that steric interactions are dominant in determining the structure of buried residues, even in the TM proteins. Thus, we find that the structure of buried residues in TM is similar to that for core residues in soluble proteins.