The Mona Lisa Molecule
February 28, 1953, Cambridge, England
February 28, 1953
1. Taking the clues from the diary entry, speculate on what Francis
Crick and James Watson had discovered.
2. Why do you think that he specifically mentioned that they had
“discovered the secret of life itself”?
February 28, 1953, Cambridge, England continued...
February 28, 1953 – Stop 2
3. Why was it important to solve the structure of DNA? (Hint: Type DNA in a
search engine on the internet to try and figure out the answer to this
question.)
4. How do you think that solving the structure of DNA could move the field
of genetics forward? (Hint: This site would be helpful in answering this question.)
5. With the aid of the information on the following websites, explain how
the Hershey-Chase experiment conclusively proved that DNA and not
protein was the genetic material.
Older Diary Entries
Early October 1951, Cambridge, England
6. What is “model building”? How can this technique be used to solve the
structure of biological molecules? (Hint: Discuss both computational
model building and physical model building; this article is useful)
7. Use the following websites to help you describe the “bare bones” basic principle behind X-ray diffraction.
Franklin’s X-ray diffraction, explanation of X-ray pattern.
X-Ray Diffraction Techniques. Dissemination of IT for the Promotion of Materials Science (DoITPoMS)
8. Explain very simply how the X-ray diffraction process aids in solving structures of biological molecules.
9. Compare and contrast the two techniques above (model building and X-ray crystallography) and discuss their usefulness in structure determination of biological molecules.
A Structure for Deoxyribose Nucleic Acid
J. D. Watson and F. H. C. Crick (1)
April 25, 1953 (2), Nature (3), 171, 737-738
We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.
A structure for nucleic acid has already been proposed by Pauling (4) and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons:
(1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other.
(2) Some of the van der Waals distances appear to be too small.
Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.
The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis. They are joined together in pairs, a single base from one chain being hydroden-bonded to a single base from the other chain, so that the two lie side by side with identical z-coordinates. One of the pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6.
If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine) (9).
In other words, if an adenine forms one member of a pair, on either chain, then on these assumptions the other member must be thymine; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then the sequence on the other chain is automatically determined.
We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid (5). This structure has two helical chains each coiled round the same axis (see diagram). We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining beta-D-deoxyribofuranose residues with 3',5' linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed helices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions (6) . Each chain loosely resemblesFurberg's2 model No. 1 (7); that is, the bases are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it is close to Furberg's "standard configuration," the sugar being roughly perpendicular to the attached base. There is a residue on each every 3.4 A. in the z-direction. We have assumed an angle of 36° between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10 A. As the phosphates are on the outside, cations have easy access to them.
The structure is an open one, and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.
It has been found experimentally3,4 that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.
It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose, as the extra oxygen atom would make too close a van der Waals contact.
The previously published X-ray data5,6 on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications (10). We were not aware of the details of the results presented there when we devised our structure (11), which rests mainly though not entirely on published experimental data and stereochemical arguments.
It has not escaped our notice (12) that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
Full details of the structure, including the conditions assumed in building it, together with a set of coordinates for the atoms, will be published elsewhere (13).
End Part 1
October/December 1952
Late October 1951 – December 1952
10. Describe the building blocks of DNA in detail. (Hint: This webpage on
DNA structure will help you)
11. Define Chargaff’s Laws
12. Why were Chargaff’s Laws important in regards to solving the structure
of DNA?
Late December 1952
13. What critical pieces of information did Watson and Crick gather from the
new X-ray crystallographic pictures of B-DNA?
14. Why was the pictures called photo 51? Who took this picture? Use the
diary and the following website to help you: “The Anatomy of Photo 51”
15. Do you think that Photo 51/Rosalind’s X-ray diffraction data was crucial
to solving the structure of DNA? Why/why not?
February/April 1953
16. Answer the following basic questions regarding the structure of DNA:
a. Name the type of bond that holds the two strands of DNA together
b. Compare the components of a nucleotide versus that of a nucleoside
c. What is meant by “antiparallel helix” as it pertains to DNA?
d. Where is a glycosidic bond located in DNA?
e. Which component of DNA imparts a negative charge to the molecule?
f. Write down the complementary strand of this DNA sequence:
5’ a t t t a g g g g c g a 3’
17. Use internet resources/articles/your textbook to determine how the
structure from the 1953 paper has been corrected in recent times (Hint:
you may use this resource to help you)
18. Create a timeline of key events leading up to the solving the correct
structure of DNa starting from the discovery of DNA as the genetic
material (you may use the following website to help you)
19. Explain this statement in detail and its underlying implications: “It has
not escaped our notice that the specific pairing we have postulated
immediately suggests a copying mechanism for the genetic material.”
December 10, 1962 - Stockholm, Sweden
20. What were Rosalind Franklin’s contributions to discovering the structure of DNA?
21. Do you think that the structure of DNA could have been solved without Rosalind’s X-ray diffraction data?