 Because protein function is determined by its shape and the physiochemical properties of its exposed surface, it is important to create an accurate model for protein/ligand interaction studies.The problem arises often in homology modeling, where the tertiary structure of an amino acid sequence is predicted based on a sequence alignment to a "template", or a second sequence whose structure is known.Because loops have highly variable sequences even within a given structural motif or protein fold, they often correspond to unaligned regions in sequence alignments; they also tend to be located at the solvent-exposed surface of globular proteins and thus are more conformationally flexible.