Loop modeling

Loop modeling is a problem in protein structure prediction requiring the prediction of the conformations of loop regions in proteins without the use of a structural template. 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. Consequently, they often cannot be modeled using standard homology modeling techniques. More constrained versions of loop modeling are also used in the data fitting stages of solving a protein structure by X-ray crystallography, because loops can correspond to regions of low electron density and are therefore difficult to resolve.

Regions of a structural model that were predicted by loop modeling tend to be much less accurate than regions that were predicted using template-based techniques. The extent of the inaccuracy increases with the number of amino acids in the loop. The loop amino acids' side chains dihedral angles are often approximated from a rotamer library, but can worsen the inaccuracy of side chain packing in the overall model. Andrej Sali's homology modeling suite MODELLER includes a facility explicitly designed for loop modeling by a satisfaction of spatial restraints method.

References

• Mount DM. (2004). Bioinformatics: Sequence and Genome Analysis 2nd ed. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY.
• Chung SY, Subbiah S. (1996.) A structural explanation for the twilight zone of protein sequence homology. Structure 4: 1123–27.

External links

• MODLOOP, public server for access to MODELLER's loop modeling facility