Patent ID: 6721664
Filing Date: 2004-04-13
Classification: G06K

Abstract:
A method for modifying an electron density map of an experimental crystallographic structure having protein regions and solvent regions to increase a likelihood function that an electron density map derived from experimentally observed structure factors for the experimental crystallographic structure represents the experimental crystallographic structure comprising:(a) obtaining x-ray data from the experimental crystallographic structure; (b) processing the x-ray data to output a first set of structure factors for the experimental crystallographic structure and a concomitant first experimental electron density map; (c) selecting a model crystallographic structure having known crystal structure model information; (d) processing the model information to output a model electron density map and model probability distributions for true electron density over protein and solvent regions of the model electron density map; (e) selecting at least one structural motif that may be associated with the experimental crystallographic structure and processing the structural motif to output a motif template electron density map for the at least one structural motif; (f) searching the first experimental electron density map to locate probable matches with the template electron density map; (g) selecting at least one structural motif that has a probable match within the first experimental electron density map, processing the at least one structural motif to output a motif probability distribution for true electron density within the at least one structural motif, and combining the motif probability distribution with the model probability distribution to provide a combined model electron density map with a combined model electron probability distribution for each of the protein regions and the solvent regions; (h) estimating probabilities from the combined model electron probability distribution that each point in the first experimental electron density map represents the experimental crystallographic structure; (i) evaluating how the probabilities of step (h) would change if electron density at each point in the first experimental electron density map changes: (j) evaluating how an overall log-likelihood of the first experimental electron density map changes for a change in each experimental structure factor value; (k) estimating a log-likelihood of any value of each structure factor as a sum of a log-likelihood of the combined model electron density map and a log-likelihood of having observed the experimental data given that value of each structure factor to provide a new probability distribution for each experimental crystallographic structure factor to form a new set of experimental structure factors and a concomitant updated experimental electron density map; (l) repeating steps (h)-(k), where the first experimental electron density map is the updated experimental electron density map, until no further changes occur in values for the experimental structure factors to form a set of final experimental structure factors; and (m) forming a modified experimental electron density map from the set of final experimental structure factors.