Positioning of proteins in membranes: A computational approach

• Published in: Protein science Vol. 15; no. 6; pp. 1318 - 1333
• Main Authors: Lomize, Andrei L., Pogozheva, Irina D., Lomize, Mikhail A., Mosberg, Henry I.
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.06.2006
• Subjects: Amino Acids - chemistry; Cell Membrane - chemistry; Cell Membrane - metabolism; channel; Computer Simulation; Databases, Protein; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; membrane protein; Membrane Proteins - chemistry; Membrane Proteins - metabolism; modeling; Models, Molecular; Protein Conformation; receptor; rhodopsin; tilt; transporter
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.062126106

A new computational approach has been developed to determine the spatial arrangement of proteins in membranes by minimizing their transfer energies from water to the lipid bilayer. The membrane hydrocarbon core was approximated as a planar slab of adjustable thickness with decadiene‐like interior and interfacial polarity profiles derived from published EPR studies. Applicability and accuracy of the method was verified for a set of 24 transmembrane proteins whose orientations in membranes have been studied by spin‐labeling, chemical modification, fluorescence, ATR FTIR, NMR, cryo‐microscopy, and neutron diffraction. Subsequently, the optimal rotational and translational positions were calculated for 109 transmembrane, five integral monotopic and 27 peripheral protein complexes with known 3D structures. This method can reliably distinguish transmembrane and integral monotopic proteins from water‐soluble proteins based on their transfer energies and membrane penetration depths. The accuracies of calculated hydrophobic thicknesses and tilt angles were ∼1 Å and 2°, respectively, judging from their deviations in different crystal forms of the same proteins. The hydrophobic thicknesses of transmembrane proteins ranged from 21.1 to 43.8 Å depending on the type of biological membrane, while their tilt angles with respect to the bilayer normal varied from zero in symmetric complexes to 26° in asymmetric structures. Calculated hydrophobic boundaries of proteins are located ∼5 Å lower than lipid phosphates and correspond to the zero membrane depth parameter of spin‐labeled residues. Coordinates of all studied proteins with their membrane boundaries can be found in the Orientations of Proteins in Membranes (OPM) database:http://opm.phar.umich.edu/.