Energy of stabilization of the right-handed beta alpha beta crossover in proteins.

An explanation in terms of conformational energies is provided for the observed nearly exclusive preference of the beta alpha beta structure for forming a right-handed, rather than a left-handed, crossover connection. Conformational energy computations have been carried out on a model beta alpha beta structure, consisting of two six-residue Val beta-strands and of a 12-residue Ala alpha-helix, connected by two flexible four-residue Ala links to the strands. The energy of the most favorable right-handed crossover is 15.51 kcal/mol lower than that of the corresponding left-handed cross-over. The right-handed crossover is a strain-free structure. Its energy of stabilization arises largely from the interactions of the two beta-strands with one another and with the alpha-helix. On the other hand, the left-handed crossover is either disrupted after energy minimization or it remains conformationally strained, as indicated by an energetically unfavorable left twisting of the beta-sheet and by the presence of high-energy local residue conformations. In the energetically most favorable right-handed crossover, the right twisting of the beta-sheet and its manner of interacting with the alpha-helix are identical with those computed earlier for isolated beta-sheets and for packed alpha/beta structures. This result supports a proposed principle that it is possible to account for the main features of frequently occurring structural arrangements in globular proteins in terms of the properties of their component structural elements.