α‐Helices are peculiar atomic arrangements characterizing protein structures. Their occurrence can be used within crystallographic methods as minimal a priori information to drive the phasing process towards solution. Recently, brute‐force methods have been
developed which search for all possible positions of α‐helices in the crystal cell by molecular replacement and explore all of them systematically. Knowing the α‐helix orientations in advance would be a great advantage for this kind of approach. For this purpose,
a fully automatic procedure to find α‐helix orientations within the Patterson map has been developed. The method is based on Fourier techniques specifically addressed to the identification of helical shapes and operating on Patterson maps described in spherical coordinates. It
supplies a list of candidate orientations, which are then refined by using a figure of merit based on a rotation function calculated for a template polyalanine helix oriented along the current direction. The orientation search algorithm has been optimized to work at 3 Å resolution,
while the candidates are refined against all measured reflections. The procedure has been applied to a large number of protein test structures, showing an overall efficiency of 77% in finding α‐helix orientations, which decreases to 48% on limiting the number of candidate solutions
(to 13 on average). The information obtained may be used in many aspects in the framework of molecular‐replacement phasing, as well as to constrain the generation of models in computational modelling programs. The procedure will be accessible through the next release of IL MILIONE
and could be decisive in the solution of new unknown structures.