Molecular Configuration of Nucleic Acids 



M. H. F. WiLKINS 



]\IRC Biophysics Research Unit, 



Physics Department, King's College, 



London, England 



Need for certainty in the structure determination of DNA 



Molecular theory of replication of genetic material and of mutation is 

 based on the structure of DNA. Since the ideas of Watson and Crick 

 concerning DNA are so aesthetically attractive and are now being extended 

 in many ways to create almost a whole subject of nucleic acid biology (e.g. 

 the structures of RNA's with various functions in protein synthesis are 

 being derived by analogy with DNA), it is important that these ideas do 

 not become a dogma and that alternatives are not ignored. It is also desirable 

 that a stage be reached where the structure of DNA can no longer be 

 regarded as hypothetical. It is essential therefore that the structure be 

 placed on a sound basis of experimental fact. 



It is generallv agreed that DNA consists of two polynucleotide chains 

 linked together bv hvdrogen bonds between adenine and thymine and 

 between guanine and cytosine. It is, however, still a somewhat open 

 question whether the hydrogen bonding scheme in the base pairs is that 

 proposed by Watson and Crick or has some other form. Valuable evidence 

 supporting the Watson Crick scheme is supplied by the studies of enzymic 

 synthesis of DNA (e.g. Josse and Romberg [i]) and evidence in favour is 

 also given by studies of complexes of synthetic polyribonucleotides [2]. I 

 wish to discuss here, however. X-ray diffraction data on DNA itself and 

 the extent to which these data provide an exact structure for DNA and 

 give a unique solution. 



Difficulties in the X-ray structure analysis of DNA 



There are two main difficulties in studying DNA by means of X-ray 

 difl'raction. First, DNA, like other chain polymer molecules, does not 

 form single crystals. The advantage of single crystals is that they enable 

 diffraction to be separated in all directions in three dimensions. Second, 

 the resolving power of the data has until very recently been insufficient to 

 show individual atoms in the structure. The first difficulty has to a large 

 extent been overcome : the DNA molecule is highly regular and fibres 



