A. N. Adhikari, J. Peng, M. Wilde, J. Xu, K. F. Freed, T. R. Sosnick, "Modeling Large Regions in Proteins: Applications to Loops, Termini and Folding," Protein Science, vol. 21, no. 1, 2011, pp. 107-121. Also Preprint ANL/MCS-P1976-1111, November 2011. [pdf]
Template-based methods for predicting protein structure provide models for a significant portion of the protein but often contain insertions or chain ends (InsEnds) of indeterminate conformation. The local structure prediction problem entails modeling the InsEnds onto the rest of the protein. A well known limit involves predicting loops of ≤ 12 residues in crystal structures. InsEnds, however, may contain as many as ~ 50 amino acids, and the template-based model of the protein itself may be imperfect. To address these challenges, we present a free modeling method for predicting the local structure of loops and large InsEnds in both crystal structures and template-based models. The approach uses single amino acid torsional angle pivot moves of the protein backbone with a Cβ level representation. Nevertheless, our accuracy for loops is comparable to existing methods. We also apply a more stringent test, the blind structure prediction and refinement categories of the CASP9 tournament, where we improve the quality of several homology based models by modeling InsEnds as long as 45 amino acids, sizes generally inaccessible to existing loop prediction methods. Our approach ranks as one of the best groups in the CASP9 refinement category that involves improving template-based models so that they can function as molecular replacement models to solve the phase problem for crystallographic structure determination.