OWLS is a modeling software package for homology or comparative modeling of protein 3D structures. It uses a comparative modeling methodology to automatically generate a refined 3D homology model of a protein sequence containing all non-hydrogen atoms, given a sequence alignment to a known 3D protein structure. Loops in the sequence are connected by OWL using state-of-the-art fragment assembly technology, also available in FALCON, based on an all-atom energy function and a new conditional random field sampling technique. Side chains are modeled by a new tree-decomposition approach, fast and accurately.