Abstract
A new potential energy function representing the conformational preferences of sequentially local regions of a protein backbone is presented. This potential is derived from secondary structure probabilities such as those produced by neural network-based prediction methods. The potential is applied to the problem of remote homolog identification, in combination with a distance-dependent inter-residue potential and position-based scoring matrices. This fold recognition jury is implemented in a Java application called JThread. These methods are benchmarked on several test sets, including one released entirely after development and parameterization of JThread. In benchmark tests to identify known folds structurally similar to (but not identical with) the native structure of a sequence, JThread performs significantly better than PSI-BLAST, with 10% more structures identified correctly as the most likely structural match in a fold library, and 20% more structures correctly narrowed down to a set of five possible candidates. JThread also improves the average sequence alignment accuracy significantly, from 53% to 62% of residues aligned correctly. Reliable fold assignments and alignments are identified, making the method useful for genome annotation. JThread is applied to predicted open reading frames (ORFs) from the genomes of Mycoplasma genitalium and Drosophila melanogaster, identifying 20 new structural annotations in the former and 801 in the latter.
