MOLECULAR CONFIGURATION OF NUCLEIC ACIDS 



structure of DNA. Crick was working on helical protein structure and was 

 interested in what controlled protein synthesis. Pauling and Corey, by their 

 discovery of the protein a-hclix, had shown that precise molecular model- 

 building was a powerful analytical tool in its own right. The X-ray data 

 from DNA were not so complete that a detailed picture of DNA structure 

 could be derived without considerable aid from stereochemistry. It was 

 clear that the X-ray studies of DNA needed to be complemented by pre- 

 cise molecular model-building. In our laboratory we concentrated on am- 

 plifying the X-ray data. In Cambridge, Watson and Crick built molecular 

 models. 



The paradox of the regularity of the DNA molecule 



The sharpness of the X-ray diffraction patterns of DNA showed that DNA 

 molecules were highly regular - so regular that DNA could crystallize. The 

 form of the patterns gave clear indications that the molecule was helical, the 

 polynucleotide chains in the molecular thread being regularly twisted. It was 

 known, however, that the purines and pyrimidines of various dimensions 

 were arranged in irregular sequence along the polynucleotide chains. How 

 could such an irregular arrangement give a highly regular structure? This 

 paradox pointed to the solution of the DNA structure problem and was 

 resolved by the structural hypothesis of Watson and Crick. 



The Helical Structure of the DNA Molecule 



The key to DNA molecular structure was the discovery by Watson and 

 Crick 13 that, if the bases in DNA were joined in pairs by hydrogen-bonding, 

 the overall dimensions of the pairs of adenine and thymine and of guanine 

 and cytosine were identical. This meant that a DNA molecule containing 

 these pairs could be highly regular in spite of the sequence of bases being 

 irregular. Watson and Crick proposed that the DNA molecule consisted of 

 two polynucleotide chains joined together by base-pairs. These pairs are 

 shown in Fig. 2. The distance between the bonds joining the bases to the 

 deoxyribosc groups is exactly (within the uncertainty of 0.1 A or so) the 

 same for both base-pairs, and all those bonds make exactly (within the 

 uncertainty of i° or so) the same angle with the line joining the C x atoms 

 of the deoxyribose (see Fig. 2). As a result, if two polynucleotide chains are 



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