Patent ID: 6931329

Claim:
A method for improving an electron density map of an experimental crystal structure, comprising the steps of: (a) forming a model electron density map from known crystallographic information of an exemplary model crystal structure; (b) forming model histograms of model electron densities in identified protein and solvent regions of the model electron density map; (c) fitting a model probability distribution function defined by p ⁡ ( ρ ⁢ ⁢ T ) = ∑ k ⁢ w k ⁢ exp ⁢ { - ⁢ ( ρ - c k ) 2 2 ⁢ σ k 2 } to the model histograms, where k is separately indexed over the protein and solvent regions of the model map, p(ρ T ) is a probability of an electron density at a point, w k is a normalization factor, ρ is electron density, c k is a mean value of ρ, and σ k is a variance of ρ, where the fitting determines the coefficients w k , c k , and σ k ; (d) determining a set of experimental structure factors from x-ray diffraction data for the experimental crystal structure and forming an experimental electron density map; (e) forming separate experimental histograms of experimental electron densities over protein and solvent regions of the model electron density map; (f) fitting an experimental probability distribution function defined by p ⁡ ( ρ ⁢ ⁢ T ) = ∑ k ⁢ w k ⁢ exp ⁢ { - ⁢ ( ρ - β ⁢ ⁢ c k ) 2 2 ⁢ ( β ⁢ ⁢ σ k 2 + σ map 2 ) } to separate protein and solvent regions of the experimental histograms, where β is an expectation that an experimental value of ρ is less than a true value and σ map is a variance, where the fitting determines the coefficients β and σ map ; (g) determine the overall experimental log-likelihood of the electron density in the protein and solvent regions of the experimental map from the experimental probability distribution function LL (ρ( x,{F h }))=ln[ p (ρ( x )| PROT ) p PROT ( x )+ p (ρ( x )| SOLV ) p SOLV ( x )] where p PROT (x) is the probability that x is in the protein region and p(ρ(x)|PROT) is the conditional probability for ρ(x) given that x is in the protein region, and p SOLV (x) and p(ρ(x)|SOLV) are the corresponding quantities for the solvent region; (h) determine how the experimental log-likelihood of the electron density of the protein and solvent regions of the structure factor experimental electron density map would change as each experimental structure factor changes to output a revised log-likelihood of any value of each experimental structure factor; (i) forming from the revised log-likelihood of experimental structure factor values a new set of structure factors; and (j) forming a revised experimental electron density map from the revised structure factors.