In order to predict the structure of α-helical coiled-coil proteins from their sequences, it is necessary to know how the side-chains pack in the interface between the α-helical strands. Since in α-fibrous proteins leucine is the most common residue at both theaanddpositions of the heptad repeat, which form the inner core of the interface, we determined the lowest-energy conformation for a two-stranded coiled-coil with the sequence (LAALAAA)5. Coiled-coils were constructed using the Crick equations with a range of pitches, major helical radii and relative rotations of the two strands, and with different starting side-chain conformations. On energy minimisation, convergence occurred to a small number of structures. The lowest-energy coiled-coil had 2-fold rotational symmetry, an average pitch of 131 Å and an average radius of 4.52 Å; the leucine side-chain conformations werettandg+tat theaanddpositions.This coiled-coil was used as a former to determine the lowest-energy side-chain conformations for the 63 combinations ofaanddresidues that occur in the repeating heptad sequence of rat skeletal myosin. The leucine residues at theaanddpositions of the central heptad were replaced by thea-dpair of interest and molecular dynamics simulations performed to allow the side-chains of these residues to explore conformational space. The lowest-energy side-chain conformation of a residue at anaordposition depends on the nature of the partnering residue, consistent with the fact that these side-chains pack against one another. In most cases the lowest-energy structure was symmetric but in a few cases the side-chains were asymmetrically disposed in the two strands. The local pitch is very sensitive to the nature of the residues in the inner core and varies over a twofold range. In contrast, the radius and rotation of the two strands were relatively insensitive to sequence.