Simulated annealing applied to crystallographic structure refinement

Simulated annealing has greatly improved the efficiency of crystallographic refinement. However, simulated annealing refinement alone is still insufficient to automatically refine a crystal structure without human intervention. Thus, crystallographic refinement of macromolecules proceeds in a series of steps, each of which consists of simulated annealing or minimization of E (Eq. 1) followed by refitting the model structure to difference electron density maps with interactive computer graphics [64]. During the final stages of [figure omitted] refinement, solvent molecules are usually included and alternate conformations for some atoms or residues in the protein may be introduced. With currently available computing power, tedious manual adjustments using computer graphics to display and move positions of atoms of the model in the electron density maps represent the rate-limiting step in the refinement process. The availability of high-performance computers has opened the door for “experimentation” with new mathematical techniques such as simulated annealing. We can expect that with ever increasing computing power and the application of novel mathematical algorithms the crystallographic structure determination process for macromolecules could be fully automated in the near future.