Quantum mechanical/X-ray crystallography diagnostic for proteins
AssigneeQuantumBio Inc.
InventorsLance Michael Westerhoff, Oleh Y. Borbulevych, Roger Isaac Martin
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Abstract
An analytic method for improving the efficiency in identifying protein molecular effect information using low resolution x-ray crystallography, by selecting and imaging a protein sample with low resolution x-ray crystallography and assaying the data thus generated as to local ligand strain energy value, followed by calculating a real-space difference density Z for each element and compiling ZDD data therefrom, followed by determining the true protomer/tautomer state of the protein sample by calculating Scorei according to the following equation so that the highest Scorei signifies the molecular effect information: Scorei={((ZDDi−μZDD)/σZDD)+((SEi−σSE)/σSE)}.
Claims4
An analytic method more efficiently to identify conformational, protonation, or solvent effect information from a real world molecule of interest by using low resolution x-ray crystallography, comprising the steps of:
- a) selecting an aliquot of a real world molecule sample as a molecule to be diagnosed;
- b) imaging said molecule by low resolution x-ray crystallography and collecting a quantity of crystallography data generated thereby;
- c) assaying x-ray density within said crystallography data and creating from said crystallography data thus assayed a population set containing a plurality of set elements consisting of one or more of conformational, protonation or solvent effect information of said real world molecule;
- d) determining a local ligand strain energy value SE for each of said elements;
- e) determining ZDD for each of said elements by calculating a real-space difference density Z for each element and compiling ZDD data therefrom;
- and f) selecting a single element from among said elements that represents the true conformational, protonation or solvent effect information for at least one moiety of said molecule by calculating Scorei according to the following equation,
- Scorei={((ZDDi−μZDD)/σZDD)+((SEi−σSE)/σSE)}
- wherein the highest Scorei obtained for said population corresponds to the best conformational, protonation or solvent effect form “i” that fits both SE and ZDD criteria, so that Scorei when output to a user identifies the element from said population that most closely corresponds with said real world molecule thus diagnosed with increased time efficiency using said low resolution x-ray crystallography compared to the same method using atomic resolution x-ray crystallography.
An analytic method to identify conformational, protonation, or solvent effect information from a real world molecule of interest by using low resolution x-ray crystallography having a maximum resolution of 1.1 angstrom, comprising the steps of:
- a) selecting an aliquot of a real world molecule sample as a molecule to be diagnosed;
- b) imaging said molecule by low resolution x-ray crystallography and collecting a quantity of crystallography data generated thereby;
- c) assaying x-ray density within said crystallography data and creating from said crystallography data thus assayed a population set containing a plurality of set elements consisting of one or more of conformational, protonation or solvent effect information of said real world molecule;
- d) determining a local ligand strain energy value SE for each of said elements;
- e) determining ZDD for each of said elements by calculating a real-space difference density Z for each element and compiling ZDD data therefrom;
- and f) selecting a single element from among said elements that represents the true conformational, protonation or solvent effect information for at least one moiety of said molecule by calculating Scorei according to the following equation,
- Scorei={((ZDDi−μZDD)/σZDD)+((SEi−σSE)/σSE)}
- wherein the highest Scorei obtained for said population corresponds to the best conformational, protonation or solvent effect form “i” that fits both SE and ZDD criteria, so that Scorei when output to a user identifies the element from said population that most closely corresponds with said real world molecule thus diagnosed with increased time efficiency using said low resolution x-ray crystallography compared to the same method using atomic resolution x-ray crystallography.
Dependencies are inferred from the claim text.