Figure 1.

Workflow of fc-rDG/DDD calculations: (a) based on the known molecular constitution in an arbitrary configuration (and conformation), a set of holonomic intramolecular distances including bond lengths (1,2-distances), angles (1,3-distances), and torsions (1,4-distances), excluded van der Waals volumes, and NOE/ROE-derived distance limits between all atom–atom pairs $i,j$ defines boundary conditions for computing molecular structures similar to using a model construction kit. (b) Using this basic scaffolding information, initial guess structure models of arbitrary configuration and conformation are generated by a “metrization” procedure in 4D space. (c) These models are subsequently refined through an automated sequence of simulated annealing steps in 4D and 3D space under the restraints of experimental NOE/ROE distance limits, by which finally the correct configuration evolves as the best-fit structures of the lowest pseudo energy (total error).