A new article by the Schulten group (University of Illinois at Urbana-Champaign, USA) employs MDFF in an novel way, namely to retrieve atomistic information from a coarse-grained model of myosin.
Formation of salt bridges mediates internal dimerization of myosin VI medial tail domain.
HyeongJun Kim, Jen Hsin, Yanxin Liu, Paul R. Selvin, and Klaus Schulten. Structure, 18, 1443-1449, 2010.
The unconventional motor protein, myosin VI, is known to dimerize upon cargo-binding to its C-terminal end. It has been shown that one of its tail domains, called the medial tail domain, is a dimerization region. The domain contains an unusual pattern of alternating charged residues and a few hydrophobic residues. To reveal the unknown dimerization mechanism of the medial tail domain, we employed molecular dynamics and single-molecule experimental techniques. Both techniques suggest that the formation of electrostatic-based inter-helical salt bridges between oppositely-charged residues is a key dimerization factor. For the dimerization to occur, the two identical helices within the dimer don't bind in a symmetric fashion, but rather with an off-set of about one helical repeat. Calculations of the dimer-dissociation energy find the contribution of hydrophobic residues to the dimerization process to be minor; they also find that the asymmetric homodimer state is energetically favorable over a state of separate helices.
