Patterns in the complementary determining regions of immunoglobulins (CDRs).

An analysis of the frequency of use of amino acids on the CDR-1 and CDR-2 of 1500 immunoglobulins showed that the frequencies of amino acids in different positions could be fitted by two types of distribution. For some positions the frequencies were fitted by an inverse power law and for other positions by an exponential distribution. In order to see whether the more frequently used amino acids for specific positions had physicochemical properties or attributes in common, they were clustered using an algorithm normally applied to artificial intelligence problems. It was found that the amino acids in those positions fitted by the inverse power law have similar hydrophobicity and volume, which are commonly attributes of amino acids in structural positions. Thus, if these positions are critical to maintaining the structural features of the CDR domains, the rest of the positions should be either properly involved in the recognition process or irrelevant. The frequencies of amino acids in these recognition positions were fitted by the exponential law, and it was found by the clustering analysis that these amino acids share properties of a more general type, such as capability of forming hydrogen bonds, polarity, etc. This suggests that at least part of the recognition mechanism requires general properties rather than specific amino acids. Amino acids sharing the required attributes for each one of these positions are then used with random frequency.