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The interaction of transmembrane alpha-helices is promoted by a detailed fit between two helical surfaces, which results in close packing and van der Waals interactions of amino acid side chains between two helices. Recent studies additionally indicate an important role of hydrogen bonding for mediating and stabilizing transmembrane helix-helix interactions. The interplay between close packing and electrostatic interactions in influencing the specificity of helix-helix interactions on the one hand and the stability of an existing interaction on the other hand is still unknown. Here, we suggest that close packing mainly determines the specificity of a helix-helix interaction, whereas hydrogen bonding is important for stabilization of a preformed helix dimer.
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Dirk Schneider (2004) studied this question.
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