POTENTIAL USE OF REAL-SPACE REFINEMENT IN PROTEIN-STRUCTURE DETERMINATION

Through testing refinement protocols using free R-factor estimates of model quality, it is shown that real-space refinement can be a useful addition to conventional reciprocal-space refinement, even for protein structures with poor electron-density maps derived from multiple isom orphous replacement. By alternating real- and reciprocal-space refinem ents, starting with an experimental map, then calculating 2F(o) - F-c maps, it is demonstrated with the structure of HMG-CoA reductase, that quick automatic refinement can yield a model with a free R factor 1.5 % better than exhaustive reciprocal-space refinement, and within 1% of a model that was interactively rebuilt and refined repeatedly.