Prediction of membrane-protein topology from first principles.
The current best membrane-protein topology-prediction methods are typically based on sequence statistics and contain hundreds of parameters that are optimized on known topologies of membrane proteins. However, because the insertion of transmembrane helices into the membrane is the outcome of molecular interactions among protein, lipids and water, it should be possible to predict topology by methods based directly on physical data, as proposed >20 years ago by Kyte and Doolittle. Here, we present two simple topology-prediction methods using a recently published experimental scale of position-specific amino acid contributions to the free energy of membrane insertion that perform on a par with the current best statistics-based topology predictors. This result suggests that prediction of membrane-protein topology and structure directly from first principles is an attainable goal, given the recently improved understanding of peptide recognition by the translocon.
Bernsel
Andreas
A
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Viklund
Håkan
H
Falk
Jenny
J
Lindahl
Erik
E
von Heijne
Gunnar
G
Elofsson
Arne
A
D000818:Animals; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism*; D002627:Chemistry, Physical / Q000379:methods; D030562:Databases, Protein; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D015233:Models, Statistical; D011336:Probability; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D040901:Proteomics / Q000379:methods; D020539:Sequence Analysis, Protein; D013816:Thermodynamics
D008055:Lipids; D008565:Membrane Proteins