Reconstruction of protein form with X-ray solution scattering and a genetic algorithm

We have reconstructed, from experimental similar to 2 nm resolution X-ray s olution scattering profiles, the corresponding shapes and sizes of myoglobi n, troponin C, spermadhesin PSP-I/PSP-II, chymotrypsinogen A, superoxide di smutase, ovalbumin, tubulin, nitrite reductase, catalase, the structural ch ange of troponin C upon dissociation of the two high affinity Ca2+, and the solution model structure of a tandem pair of fibronectin type III cytoplas mic domains of integrin alpha 6 beta 4 before determination of its crystal structure. To this purpose we have designed a new genetic algorithm which g radually explores a discrete search space and evolves convergent models mad e of several hundred beads (down to 0.3 nm radius) best fitting the scatter ing profile upon Debye calculation, without geometrical constraints or pena lty for loose beads. This is a procedure of effective numerical transformat ion of the one-dimensional scattering profiles into three-dimensional model structures. The number of beads in models is correlated with the protein m olecular mass (with one exception). The shape and approximate dimensions of each protein have been retrieved by a set of ten solution models, essentia lly superimposable with the available crystal structures. (C) 2000 Academic Press.