  Structure predictions of helical membrane proteins have been designed to take
advantage of the structural autonomy of secondary structure elements, as
postulated by the two-stage model of Engelman and Popot. In this context, we
investigate structure calculation strategies for two membrane proteins with
different functions, sizes, aminoacid compositions, and topologies: the
glycophorin A homodimer (a paradigm for close inter-helical packing in membrane
proteins) and aquaporin (a channel protein). Our structure calculations are
based on two alternative folding schemes: a one-step simulated annealing from
an extended chain conformation, and a two-step procedure inspired by the
grid-search methods traditionally used in membrane protein predictions. In this
framework, we investigate rationales for the utilization of sparse NMR data
such as distance-based restraints and residual dipolar couplings in structure
calculations of helical membrane proteins.
