Simulation of helix association in membranes: modeling the glycophorin A transmembrane domain

A study to predict the transmembrane structure of glycophorin A (GpA), a dimeric membrane protein is presented. The authors have developed a method to study the stability, structure, and energetics of a large number of conformations of pairs of helical proteins. The method employs molecular dynamics simulation to study the association of two helices in vacuum using an automated procedure and can be applied to any amino-acid sequence. The calculations found three conformations of the helical dimer located inside the membrane that form local energy minima of the interaction energy of the helices. Only one of the three conformations, a right-handed supercoil, is compatible with mutagenesis data. Simulations inside a lipid bilayer were performed to further refine the structure of the transmembrane region. The work shows that a combined approach of modeling and mutagenesis can be used to reveal structural information about a protein with known secondary structure.<
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