Correlation of sequence and tertiary structure in globular proteins

The x‐ray crystal structures of 19 selected proteins are examined empirically for correlations between the amino acid sequence and long‐range, tertiary conformation. There is clear evidence for preferential associations of certain types of amino acids, particularly among the hydrophobic aliphatic, aromatic, and cysteine residues. However, the likelihoods of forming these residue‐pair contacts are all less than 12%, so packing and geometric requirements must often take precedent over energetic considerations. The prediction of long‐range contacts is not substantially improved by taking into account the sequentially previous residues. The analysis of atom–atom contacts shows a similar lack of predictive ability, but the results show that a good approximation to the interresidue energy function must include different types of interactions at two or three different sites on some amino acids. Backbone–backbone long‐range interactions are relatively rare and nonspecific, whereas some “polar” side chains form hydrogen bonds from the polar groups while occasionally forming hydrophobic contacts with the remainder of the chain.