A Simulated Annealing Approach to the Search Problem of Protein Crystallography

with the srowins """ilill;"f computer power ithas become routine to perform exhaustive multi-dimensional searches in protein crystallography. Specifically, in cases where homologous or partially homologous structures are available, the initial inter-pretation of poor electron density maps is done by performing computer-intensive rotational and trans-lational searches in real space. Often such calcula-tions of the best fit between structure and map can-not even be attempted owing to the vast computing effort involved (years of MicroVAX II time). Here, the combinatorial optimization method, simulated annealing, is shown to reduce substantially the com-puting effort involved and also to permit computa-tions that are beyond the reach of current algorithms. This is illustrated with practical examples involving the structure determinations of the human histo-compatibility antigen HLA-A2 and an influenza virus hemagglutinin-sialic acid complex. 1