 Larger regions are often modeled individually using ab initio structure prediction techniques, although this approach has met with only isolated success.The rotameric states of side chains and their internal packing arrangement also present difficulties in homology modeling, even in targets for which the backbone structure is relatively easy to predict.This is partly due to the fact that many side chains in crystal structures are not in their "optimal" rotameric state as a result of energetic factors in the hydrophobic core and in the packing of the individual molecules in a protein crystal.