LOOKING AHEAD

It is now almost 200 years since Gauss, a teenager at the time, formulated his famous principle of least-squares and used it to determine, for the first time, the orbit of one of the asteroids, a problem which had defeated astronomers for years. When applied to the crystallographic phase problem, least-squares leads directly to the formulation of the minimal principle, which effectively replaces the phase problem by one of constrained global minimization. Shake-and-Bake, the computer software package which implements this formulation of the phase problem, provides a completely automatic solution of this problem. The program has solved ca two dozen structures, of which five or six had been previously unknown, with no failure. Three of these structures - gramicidin A, crambin and rubredoxin - in the 300-500 atom range, and six or seven others, in the 100-200 atom range, were all routinely solved With this background it now appears likely that, provided data to atomic resolution is available, structures having as many as 1000 atoms or more will prove to be solvable by this technique. What if only diffraction data to less than atomic resolution is available? Here the crystal ball becomes murky and the evidence less than compelling. Nevertheless, in view of recent experience, it is again conjectured that, building on existing techniques, complex structures will eventually prove to be routinely solvable, even with data to only 1.5 Angstrom resolution.