Weininger Works™ Analytics Tests
Double Blind Tests
(WEB PAGE PDF)
The analytic capabilities of Susan Weininger remain unsurpassed. Testing of analytics is accomplished by performing double-blind studies.
In carefully supervised double-blind tests Susan Weininger:
- has folded proteins to within experimentally defined accuracy from non-homologous sequence only; and
- has been able to determine how crystal structures differ from solution structures (i.e. crystallization condition artifacts).
At the time of the cheY and diphtheria toxin structure tests by Susan Weininger/Holtzman/Kilkowski, the cheY and diphtheria toxin sequences had no known homology to any other protein whose structure was solved but not released or known, respectively. A theoretical understanding of the intermolecular forces that determine the folding of a stable folded structure is necessary to evaluate (among other things):
- whether a crystal structure feature is present due to crystallization conditions (i.e. present or not present in solution);
- the stability of protein substructures and the protein itself;
- the effect of mutations; and
- the stabilizing or destabilizing effect of grafting or ligating functionality.
We believe that AI cannot independently get to a theoretical understanding of protein folding at this time or in the near future. The examples provided herein of our work are not comprehensive and are provided simply to provide an idea of the depth and breadth of our work. We have not included information related to ongoing discoveries, analyses, unpatented inventions, and any historical commercially-directed work.
 CheY documents (PDF) |
 Calmodulin documents (PDF) |
 DT documents (PDF) |
| CheY structure known but not released | Calmodulin structure with artifacts related to solution | DT toxin with no known structure |
| In April 1988, Susan Weininger† successfully competed in a double blind AAAS protein structure general challenge. Susan Weininger predicted the structure of CheY to experimentally defined accuracy from sequence only. CheY had no sequence homology to any proteins with known structures.1 | In February 1987, Susan Weininger† critiqued an x-ray structure of calmodulin for Walter Gilbert (Harvard University). Susan Weininger predicted the differences between the crystal structure and the solution structure of calmodulin. Susan Weininger predicted that the central helix in the crystallographic calmodulin structure (the “dumbbell” structure) was not structured in solution. Not matching crystallographic positions, the central helix was not graded as “correct” until later solution studies2,3 confirmed Susan Weininger's analysis. | In September 1986, Susan Weininger† correctly determined the structural correspondence between the ADP-ribosylating enzymes Exotoxin A and diphtheria toxin. There was no sequence homology between the proteins and only the structure of Exotoxin A4 was known. Susan Weininger correctly identified the glutamic acid in the diphtheria toxin active site. This was later confirmed by photoaffinity labeling. The structure of diphtheria toxin5 would be published nearly 6 years later confirming the structural correspondences between Exotoxin A and diphtheria toxin. |
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1 Stock AM, Mottonen JM, Stock JB, Schutt CE Three-dimensional structure of CheY, the response regulator of bacterial chemotaxis. Nature 1989 Feb 23; (6209):745-749. DOI: 10.1038/337745a0 PMID: 2645526 |
2 Persechini A, Kretsinger RH The central helix of calmodulin functions as a flexible tether. J Biol Chem 1988 Sep 5; 263(25):12175-12178. DOI: 10.1016/S0021-9258(18)37733-0 PMID: 3137220 3 O'Neil KT, Erickson-Viitanen S DeGrado WF Photolabeling of calmodulin with basic, amphiphilic alpha-helical peptides containing p-benzoylphenylalanine. J Biol Chem 1989 Aug 25; 264(24):14571-14578 DOI: jbc.org/article/S0021-9258(18)67441-1/pdf PMID: 2760074 |
4 Allured VS, Collier RJ, Carroll SF, McKay DB Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-1324. DOI: 10.1073/pnas.83.5.1320 PMID: 3006045 5 Choe S, Bennett MJ, Fujii G, Curmi PM, Kantardjieff KA, Collier RJ, Eisenberg D The crystal structure of diphtheria toxin. Nature 357 (6375), 216-222 (1992) DOI: 10.1038/357216a0 PMID: 1589020 |
† Susan Kilkowski (prior to June 1985) = Susan Holtzman (June 1985 – July 1993) = Susan Weininger (July 1993 to present)