Abstract
The three-dimensional structure of the signal sequence for murine kappa light chain has been calculated by using conformational energy calculations. These calculations, based on tested and reliable potential energy functions, employ a novel global search technique to identify the lowest energy structures for the hexadecapeptide signal sequence, Glu-Thr-Asp-Thr-(Leu3-Trp-Val)2-Pro-Gly.l It has been found that the core hydrophobic sequence, Leu3-Trp-Val-Leu3, adopts an alpha-helical conformation that is terminated by chain reversal conformations for the four residues, Trp-Val-Pro-Gly. The amino-terminal four residues adopt low energy conformations that are fully compatible with the succeeding alpha-helix. The immediately neighboring sequence., Asp-Thr, exists in a single lowest energy double-equatorial conformation, whereas the first two residues, Glu-Thr, can adopt a variety of low energy conformations. The calculations arrive at a highly structured and specific model for the conformation of a leader sequence, compatible with recent experimental data.
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