Ab Initio Protein Structure Prediction via a Combination of Threading, Lattice Folding, Clustering, and Structure Refinement

ABSTRACT A combination of sequence com-parison, threading, lattice, and off-lattice Monte Carlo (MC) simulations and clustering of MC trajec-tories was used to predict the structure of all (but one) targets of the CASP4 experiment on protein structure prediction. Although this method is auto-mated and is operationally the same regardless of the level of uniqueness of the query proteins, here we focus on the more difficult targets at the border of the fold recognition and new fold categories. For a few targets (T0110 is probably the best example), the ab initio method produced more accurate mod-els than models obtained by the fold recognition techniques. For the most difficult targets from the new fold categories, substantial fragments of struc-tures have been correctly predicted. Possible im-provements of the method are briefly discussed