136 LINUS PAULING 



way by a primary' process, but will be a product obtained after many steps of 

 two-stage duplication. 



The details of the process by means of which specific molecules of protein 

 are manufactured by molecules of nucleic acid, which serve as the templates 

 for their manufacture, are not yet known, but there is no reason to doubt that 

 this process takes place. There are two aspects of the structure of proteins that 

 may be differentiated. One is the ordering of amino acid residues into the proper 

 sequence in the polypeptide chain, and the other is the folding of the polypeptide 

 chain into the configuration characteristic of the native protein molecule. It is 

 likely that the principal function of the gene in the process of manufacture of a 

 protein molecule is to select the right amino acid molecules and to order their 

 residues into the right sequence in the polypeptide chain. The experiments of 

 Anson and Mirsky, showing that some proteins (haemoglobin and trypsin) thai 

 have been subjected to alkaU denaturation, causing some unfolding of the poly- 

 peptide chains, can, by proper treatment, be brought back to essentially the 

 native configuration, suggest that the process of folding of the polypeptide chains 

 into the correct configuration may occur automatically, without the help of a 

 template, after the polypeptide chains have been synthesized. 



We may ask whether or not it is possible for the genie template to function 

 perfectly in ordering amino acid residues during the process of synthesis of 

 polypeptide chains. An analysis of the forces operating between the amino acids 

 and the genie template [13] has led to the prediction that the process must 

 involve occasional errors, and that some protein molecules that are manufactured 

 should have a sequence of amino acid residues sUghtly different from that in 

 other molecules of the same protein. It is possible to make some predictions 

 about the nature of the errors. For example, it may be predicted that it is highly 

 imlikely that any amino acid residue other than a residue of glycine would occupy 

 a glycine locus in the polypeptide chain; the selection of glycine by the template 

 must involve the fitting of the hydrogen atom that serves as the side chain in 

 glycine into a cavity in the template that is just large enough to accommodate a 

 hydrogen atom, and is accordingly too small to accommodate the methyl group 

 of alanine or any other side chain, and the van der Waals repulsion energy be- 

 comes so great when atoms are brought into contact at a distance even 0-5 A 

 less than the normal van der Waals contact distance that the selectivity of this 

 template for glycine can be expected to be essentially perfect. On the other hand, 

 a part of the template that is complementary to alanine would have a cavity for 

 the methyl group that would be small enough to reject all amino acids except 

 alanine and the smaller one, glycine, and the selection of alanine rather than 

 glycine would have to be made through the operation of the greater van der 

 Waals attraction (London electronic dispersion energy) of the template for the 

 methyl group than that for the hydrogen atom; the estimated magnitude of the 

 energy difference leading to the selection of alanine rather than glycine has led 

 to the prediction that the probabiHty of an error involving the introduction of 

 glycine in an alanine locus should be as much as 5%. It may well be that the 

 calctilation of the energy difference has been made with too much caution, and 

 that the predicted probabihty of an error of this sort is no more than 1%. 



