5] Conformation of β hairpins in protein structures: Classification and diversity in homologous structures

Abstract

This chapter describes a systematic classification of β hairpins that is indicative of both the length of the polypeptide and the hydrogen bonding between the two antiparallel strands. The classification provides a useful tool to aid “modeling by homology” of protein structure. In this approach, the sequence of the “unknown” is modeled onto the three-dimensional coordinates provided by one or more homologous proteins. Comparisons of three-dimensional structures of homologous proteins demonstrate that the cores of proteins are highly conserved, although there are differences in relative positions and orientations of α helices and β strands. Insertions, deletions, and radical changes in conformation due to replacement are largely confined to the loop regions. These loops are, therefore, the most difficult to model and both knowledge-based and theoretical molecular mechanics/dynamics methods are being developed. The knowledge-based approach involves specifying the end-point geometry of the loop, its length, and sequence, and then searching in a database of known structures for loops, which fulfill these criteria. To explore the way changes in sequence are accommodated in β hairpins in known structures, a comparison has been drawn among the conformations of homologous β hairpins in several families. The data illustrates the way the hairpins move between two classes as residues are added or deleted and can adopt the common loop family structures if the sequence is appropriate.