Head-to-tail sequences and other patterns of peptide aggregation in the solid state

Abstract

Encouraged by the results of our earlier study on the occurrence and the geometrical features of head-to-tail sequences involving amino acids, which have been suggested to be of probable relevance to prebiotic polymerisation, the available crystal structures of unprotected peptides have been analysed with a view to investigating head-to-tail sequences and other patterns of peptide aggregation in the solid state. The number of available dipeptide structures is large enough to permit meaningful conclusions. The dipeptide molecules in the crystal structures can be broadly classified as extended or folded depending upon their conformations. The basic elements of dipeptide aggregation are different types of head-to-tail sequences and sequences involving hydrogen bonds with the peptide nitrogen atom as the donor, generated by periodic translations and 2₁ screw axes. Using these basic elements and the known geometrical preferences of hydrogen bonds, it is possible to construct several plausible idealized patterns, mostly two-dimensional, of dipeptide aggregation for extended as well as folded molecules. The patterns observed in crystal structures are in substantial agreement with these idealized patterns. Infinite hydrogen-bonded sequences of the type observed in dipeptide structures remain the basic elements of aggregation in the structures of higher peptides also. The present analysis shows that peptide aggregation in the solid state is controlled primarily by interactions involving main chain atoms. Also, despite the increased molecular flexibility of peptides in comparison with amino acids and the presence of additional hydrogen bonding groups in them, head-to-tail sequences remain the most important intrinsic feature not only of amino acid aggregation but of peptide aggregation as well.