Ab initio modeling of small, medium, and large loops in proteins

This study presents different procedures for ab initio modeling of peptide loops of different sizes in proteins. Small loops (up to 8-12 residues) were generated by a straightforward procedure with subsequent "averaging" over all the low-energy conformers obtained. The averaged conformer fairly represents the entire set of low-energy conformers, root mean square deviation (RMSD) values being from 1.01 Å for a 4-residue loop to 1.94 Å for an 8-residue loop. Three-dimensional (3D) structures for several medium loops (20-30 residues) and for two large loops (54 and 61 residues) were predicted using residue-residue contact matrices divided into variable parts corresponding to the loops, and into a constant part corresponding to the known core of the protein. For each medium loop, a very limited number of sterically reasonable C^α traces (from 1 to 3) was found; RMSD values ranged from 2.4 to 5.9 Å. Single C^α traces predicted for each of the large loops possessed RMSD values of 4.5 Å. Generally, ab initio loop modeling presented in this work combines elements of computational procedures developed both for protein folding and for peptide conformational analysis.