M ay 2 00 5 Structure calculation strategies for membrane proteins ; a comparison study

Typically, structure calculations 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. The assumption used in these procedures is that transmembrane helices can be reliably restrained into canonical formations. We analyze this assumption for two membrane proteins with different functions, sizes, aminoacid compositions, and topologies: glycophorin A (a homo-oligomerizing membrane coil with canonical helices) and aquaporin (a channel protein). Our structure calculation strategies are based on two alternative folding schemes: a one-step torsion angle 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.