Patent ID: 7085653
Filing Date: 2006-08-01
Classification: G06K,G16B,G16C

Abstract:
1. A method using density modification to remove atomic model bias of an electron density map representing a crystal structure of a macromolecule comprising: (a) obtaining by x-ray diffraction observed structure factor amplitudes for a plurality of reflections from the crystal structure; (b) using a starting model of the crystal structure to calculate a starting set of crystallographic phases, and combining the starting set of crystallographic phases with the observed structure factor amplitudes to form a first set of structure factors; (c) deriving an electron density map from the current set of structure factors; (d) selecting specific features of the electron density map not used in the calculation of the first set of structure factors from the group consisting of: flatness of solvent region, non-crystallographic symmetry, structural motifs, and probability distributions for electron density in solvent regions; and using the specific features to construct probability functions for electron density for each point in the electron density map; (e) evaluating the overall probability that the electron density map is correct by making a comparison between the electron density map and the probability functions for electron density for each point in the map; (f) estimating how changes in the crystallographic phase of a reflection k affect the comparison; (g) establishing crystallographic phase probability distributions from the comparisons for the possible crystallographic phases of reflection k, absent phase information from the starting model of the crystal structure: (h) repeating steps (c) through (g) as k is indexed through all of the plurality of reflections; (i) determining a set of the most probable crystallographic phases for each one of the reflections from the crystallographic phase probability distributions; and (j) deriving an updated electron density map using the observed structure factor amplitudes and the set of crystallographic phases determined to be most probable from the crystallographic phase probability distributions for each one of the reflections; (k) repeating steps (d) through (j) with the electron density map replaced with each updated electron density map until changes in the set of crystallograph phases become minimal between successive iterations to obtain a final set of crystallographic phases with minimum bias from known electron density maps; and (I) forming a final electron density map using the final set of crystallographic phases.